Jean-pierre Renou - Academia.edu (original) (raw)

Papers by Jean-pierre Renou

Research paper thumbnail of Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated β-catenin

Oncogene, 2003

β-Catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletio... more β-Catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletion of exon 3 from the endogenous β-catenin gene in differentiating mammary alveolar epithelium of the mouse results in the generation of an activated protein that lacks amino acids 5–80. This is accompanied by a loss of mammary epithelial differentiation and a transdifferentiation process to

Research paper thumbnail of Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated beta-catenin

Oncogene, Jan 17, 2003

Beta-catenin is an executor of Wnt signaling and it can control cell fate and specification. Dele... more Beta-catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletion of exon 3 from the endogenous beta-catenin gene in differentiating mammary alveolar epithelium of the mouse results in the generation of an activated protein that lacks amino acids 5-80. This is accompanied by a loss of mammary epithelial differentiation and a transdifferentiation process to squamous metaplasias. To further understand the molecular process of transdifferentiation, the expression of genes in mammary tissue was profiled in the absence and presence of activated of beta-catenin. Microarrays were generated that carry about 8500 cDNA clones with approximately 6000 obtained from mammary tissue. Mutant tissues, which had undergone either partial (TD1) or complete (TD2) squamous transdifferentiation, were compared with wild-type mammary tissue. Four groups of genes were identified. Group 1 contained genes whose expression was induced in both mutant tissues. Groups 2 and 3 co...

Research paper thumbnail of Genome-scale Arabidopsis promoter array identifies targets of the histone acetyltransferase GCN5

The Plant Journal, 2008

We have assembled approximately 20 000 Arabidopsis thaliana promoter regions, compatible with fun... more We have assembled approximately 20 000 Arabidopsis thaliana promoter regions, compatible with functional studies that require cloning and with microarray applications. The promoter fragments can be captured as modular entry clones (MultiSite Gateway format) via site-specific recombinational cloning, and transferred into vectors of choice to investigate transcriptional networks. The fragments can also be amplified by PCR and printed on glass arrays. In combination with immunoprecipitation of protein-DNA complexes (ChIP-chip), these arrays enable characterization of binding sites for chromatin-associated proteins or the extent of chromatin modifications at genome scale. The Arabidopsis histone acetyltransferase GCN5 associated with 40% of the tested promoters. At most sites, binding did not depend on the integrity of the GCN5 bromodomain. However, the presence of the bromodomain was necessary for binding to 11% of the promoter regions, and correlated with acetylation of lysine 14 of histone H3 in these promoters. Combined analysis of ChIP-chip and transcriptomic data indicated that binding of GCN5 does not strictly correlate with gene activation. GCN5 has previously been shown to be required for light-regulated gene expression and growth, and we found that GCN5 targets were enriched in early light-responsive genes. Thus, in addition to its transcriptional activation function, GCN5 may play an important role in priming activation of inducible genes under non-induced conditions.

Research paper thumbnail of hca: an Arabidopsis mutant exhibiting unusual cambial activity and altered vascular patterning

The Plant Journal, 2005

By screening a T-DNA population of Arabidopsis mutants for alterations in inflorescence stem vasc... more By screening a T-DNA population of Arabidopsis mutants for alterations in inflorescence stem vasculature, we have isolated a mutant with a dramatic increase in vascular tissue development, characterized by a continuous ring of xylem/phloem. This phenotype is the consequence of premature and numerous cambial cell divisions in both the fascicular and interfascicular regions that result in the loss of the alternate vascular bundle/fiber organization typically observed in Arabidopsis stems. The mutant was therefore designated high cambial activity (hca). The hca mutation also resulted in pleiotropic effects including stunting and a delay in developmental events such as flowering and senescence. The physiological characterization of hca seedlings in vitro revealed an altered auxin and cytokinin response and, most strikingly, an enhanced sensitivity to cytokinin. These results were substantiated by comparative microarray analysis between hca and wild-type plants. The genetic analysis of hca indicated that the mutant phenotype was not tagged by the T-DNA and that the hca mutation segregated as a single recessive locus, mapping to the long arm of chromosome 4. We propose that hca is involved in mechanisms controlling the arrangement of vascular bundles throughout the plant by regulating the auxin-cytokinin sensitivity of vascular cambial cells. Thus, the hca mutant is a useful model for examining the genetic and hormonal control of cambial growth and differentiation.

Research paper thumbnail of Cross-talk between ethylene and drought signalling pathways is mediated by the sunflower Hahb-4 transcription factor

The Plant Journal, 2006

Hahb-4 is a member of the Helianthus annuus (sunflower) subfamily I of HD-Zip proteins that is tr... more Hahb-4 is a member of the Helianthus annuus (sunflower) subfamily I of HD-Zip proteins that is transcriptionally regulated by water availability and abscisic acid. Transgenic Arabidopsis thaliana plants overexpressing this transcription factor (TF) exhibit a characteristic phenotype that includes a strong tolerance to water stress. Here we show that this TF is a new component of ethylene signalling pathways, and that it induces a marked delay in senescence. Plants overexpressing Hahb-4 are less sensitive to external ethylene, enter the senescence pathway later and do not show the typical triple response. Furthermore, transgenic plants expressing this gene under the control of its own inducible promoter showed an inverse correlation between ethylene sensitivity and Hahb-4 levels. Potential targets of Hahb-4 were identified by comparing the transcriptome of Hahb-4-transformed and wild-type plants using microarrays and quantitative RT-PCR. Expression of this TF has a major repressive effect on genes related to ethylene synthesis, such as ACO and SAM, and on genes related to ethylene signalling, such as ERF2 and ERF5. Expression studies in sunflower indicate that Hahb-4 transcript levels are elevated in mature/senescent leaves. Expression of Hahb-4 is induced by ethylene, concomitantly with several genes homologous to the targets identified in the transcriptome analysis (HA-ACOa and HA-ACOb). Transient transformation of sunflower leaves demonstrated the action of Hahb-4 in the regulation of ethylene-related genes. We propose that Hahb-4 is involved in a novel conserved mechanism related to ethylene-mediated senescence that functions to improve desiccation tolerance.

Research paper thumbnail of Walls are thin 1 (WAT1), an Arabidopsis homolog of Medicago truncatula NODULIN21, is a tonoplast-localized protein required for secondary wall formation in fibers

The Plant Journal, 2010

By combining Zinnia elegans in vitro tracheary element genomics with reverse genetics in Arabidop... more By combining Zinnia elegans in vitro tracheary element genomics with reverse genetics in Arabidopsis, we have identified a new upstream component of secondary wall formation in xylary and interfascicular fibers. Walls are thin 1 (WAT1), an Arabidopsis thaliana homolog of Medicago truncatula NODULIN 21 (MtN21), encodes a plant-specific, predicted integral membrane protein, and is a member of the plant drug/metabolite exporter (P-DME) family (transporter classification number: TC 2.A.7.3). Although WAT1 is ubiquitously expressed throughout the plant, its expression is preferentially associated with vascular tissues, including developing xylem vessels and fibers. WAT1:GFP fusion protein analysis demonstrated that WAT1 is localized to the tonoplast. Analysis of wat1 mutants revealed two cell wall-related phenotypes in stems: a defect in cell elongation, resulting in a dwarfed habit and little to no secondary cell walls in fibers. Secondary walls of vessel elements were unaffected by the mutation. The secondary wall phenotype was supported by comparative transcriptomic and metabolomic analyses of wat1 and wild-type stems, as many transcripts and metabolites involved in secondary wall formation were reduced in abundance. Unexpectedly, these experiments also revealed a modification in tryptophan (Trp) and auxin metabolism that might contribute to the wat1 phenotype. Together, our data demonstrate an essential role for the WAT1 tonoplast protein in the control of secondary cell wall formation in fibers.

Research paper thumbnail of Arabidopsis NRP1 and NRP2 Encode Histone Chaperones and Are Required for Maintaining Postembryonic Root Growth

THE PLANT CELL ONLINE, 2006

NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) is conserved from yeast to human and was proposed to act as a... more NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) is conserved from yeast to human and was proposed to act as a histone chaperone. While budding yeast contains a single NAP1 gene, multicellular organisms, including plants and animals, contain several NAP1 and NAP1-RELATED PROTEIN (NRP) genes. However, the biological role of these genes has been largely unexamined. Here, we show that, in Arabidopsis thaliana, simultaneous knockout of the two NRP genes, NRP1 and NRP2, impaired postembryonic root growth. In the nrp1-1 nrp2-1 double mutant, arrest of cell cycle progression at G2/M and disordered cellular organization occurred in root tips. The mutant seedlings exhibit perturbed expression of ;100 genes, including some genes involved in root proliferation and patterning. The mutant plants are highly sensitive to genotoxic stress and show increased levels of DNA damage and the release of transcriptional gene silencing. NRP1 and NRP2 are localized in the nucleus and can form homomeric and heteromeric protein complexes. Both proteins specifically bind histones H2A and H2B and associate with chromatin in vivo. We propose that NRP1 and NRP2 act as H2A/H2B chaperones in the maintenance of dynamic chromatin in epigenetic inheritance. 65643603 or 33-3-88614442.

Research paper thumbnail of Polycomb Repressive Complex 2 Controls the Embryo-to-Seedling Phase Transition

PLoS Genetics, 2011

Polycomb repressive complex 2 (PRC2) is a key regulator of epigenetic states catalyzing histone H... more Polycomb repressive complex 2 (PRC2) is a key regulator of epigenetic states catalyzing histone H3 lysine 27 trimethylation (H3K27me3), a repressive chromatin mark. PRC2 composition is conserved from humans to plants, but the function of PRC2 during the early stage of plant life is unclear beyond the fact that it is required for the development of endosperm, a nutritive tissue that supports embryo growth. Circumventing the requirement of PRC2 in endosperm allowed us to generate viable homozygous null mutants for FERTILIZATION INDEPENDENT ENDOSPERM (FIE), which is the single Arabidopsis homolog of Extra Sex Combs, an indispensable component of Drosophila and mammalian PRC2. Here we show that H3K27me3 deposition is abolished genome-wide in fie mutants demonstrating the essential function of PRC2 in placing this mark in plants as in animals. In contrast to animals, we find that PRC2 function is not required for initial body plan formation in Arabidopsis. Rather, our results show that fie mutant seeds exhibit enhanced dormancy and germination defects, indicating a deficiency in terminating the embryonic phase. After germination, fie mutant seedlings switch to generative development that is not sustained, giving rise to neoplastic, callus-like structures. Further genome-wide studies showed that only a fraction of PRC2 targets are transcriptionally activated in fie seedlings and that this activation is accompanied in only a few cases with deposition of H3K4me3, a mark associated with gene activity and considered to act antagonistically to H3K27me3. Up-regulated PRC2 target genes were found to act at different hierarchical levels from transcriptional master regulators to a wide range of downstream targets. Collectively, our findings demonstrate that PRC2-mediated regulation represents a robust system controlling developmental phase transitions, not only from vegetative phase to flowering but also especially from embryonic phase to the seedling stage.

Research paper thumbnail of An Integrated Genomics Approach to Define Niche Establishment by Rhodococcus fascians

PLANT PHYSIOLOGY, 2009

Chlorophyll fluorescence parameters were measured with an Imaging-PAM Chlorophyll Fluorometer (Wa... more Chlorophyll fluorescence parameters were measured with an Imaging-PAM Chlorophyll Fluorometer (Walz). Mock-inoculated controls and R. fascians-infected plants (strains D188 and D188-5) were compared in their photosynthetic capacity at 4, 7, 14, and 21 dpi. At least 15 areas of interest, over Niche Establishment by Rhodococcus fascians

Research paper thumbnail of The Cold-Induced Early Activation of Phospholipase C and D Pathways Determines the Response of Two Distinct Clusters of Genes in Arabidopsis Cell Suspensions

PLANT PHYSIOLOGY, 2005

In plants, a temperature downshift represents a major stress that will lead to the induction or r... more In plants, a temperature downshift represents a major stress that will lead to the induction or repression of many genes. Therefore, the cold signal has to be perceived and transmitted to the nucleus. In response to a cold exposure, we have shown that the phospholipase D (PLD) and the phospholipase C (PLC)/diacylglycerol kinase pathways are simultaneously activated. The role of these pathways in the cold response has been investigated by analyzing the transcriptome of cold-treated Arabidopsis (Arabidopsis thaliana) suspension cells in the presence of U73122 or ethanol, inhibitors of the PLC/diacylglycerol kinase pathway and of the phosphatidic acid produced by PLD, respectively. This approach showed that the expression of many genes was modified by the cold response in the presence of such agents. The cold responses of most of the genes were repressed, thus correlating with the inhibitory effect of U73122 or ethanol. We were thus able to identify 58 genes that were regulated by temperature downshift via PLC activity and 87 genes regulated by temperature downshift via PLD-produced phosphatidic acid. Interestingly, each inhibitor appeared to affect different cold response genes. These results support the idea that both the PLC and PLD pathways are upstream of two different signaling pathways that lead to the activation of the cold response. The connection of these pathways with the CBF pathway, currently the most understood genetic system playing a role in cold acclimation, is discussed. ).

Research paper thumbnail of Genetic Variation Suggests Interaction between Cold Acclimation and Metabolic Regulation of Leaf Senescence

PLANT PHYSIOLOGY, 2006

The extent to which leaf senescence is induced by nitrogen deficiency or by sugar accumulation va... more The extent to which leaf senescence is induced by nitrogen deficiency or by sugar accumulation varies between natural accessions of Arabidopsis (Arabidopsis thaliana). Analysis of senescence in plants of the Bay-0 3 Shahdara recombinant inbred line (RIL) population revealed a large variation in developmental senescence of the whole leaf rosette, which was in agreement with the extent to which glucose (Glc) induced senescence in the different lines. To determine the regulatory basis of genetic differences in the Glc response, we investigated changes in gene expression using Complete Arabidopsis Transcriptome MicroArray (CATMA) analysis. Genes whose regulation did not depend on the genetic background, as well as genes whose regulation was specific to individual RILs, were identified. In RIL 310, a line that does not show the typical senescence response to Glc, stress response genes, especially those responding to cold stress, were induced by Glc. We therefore tested whether cold acclimation delays senescence by reducing sugar sensitivity. In cold-acclimated plants, leaf senescence was severely delayed and Glc did not induce the typical senescence response. Together, our results suggest that cold acclimation extends rosette longevity by affecting metabolic regulation of senescence, thereby allowing vernalization-dependent plants to survive the winter period. The role of functional chloroplasts and of nitrogen and phosphate availability in this regulation is discussed.

Research paper thumbnail of Phosphatidylinositol 4-Kinase Activation Is an Early Response to Salicylic Acid in Arabidopsis Suspension Cells

PLANT PHYSIOLOGY, 2007

J.-P.R., L.T.); and Institute of Experimental Botany, v.v.i., Academy of Sciences of the Czech Re... more J.-P.R., L.T.); and Institute of Experimental Botany, v.v.i., Academy of Sciences of the Czech Republic, Prague 165 02, Czech Republic (L.B.)

Research paper thumbnail of Activation of β-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation

Oncogene, 2003

The Wnt/b-catenin signaling pathway is critical for normal mammalian development, the specificati... more The Wnt/b-catenin signaling pathway is critical for normal mammalian development, the specification of epidermal cells and neoplastic transformation of intestinal epithelium. However, precise molecular information regarding cell-specific responses to b-catenin signaling has been limited. This question was addressed using a mouse model in which exon 3 of the b-catenin gene was deleted in several cell types with loxP-mediated recombination utilizing a Cre transgene under control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). The stabilization of b-catenin in prostate epithelium resulted in hyperplasias and extensive transdifferentiation into epidermal-like structures, which expressed keratins 1 and 6, filaggrin, loricrin and involucrin. The cell-specific loss of NKCC1 protein and reduced nuclear Stat5a is further suggestive of a loss of prostate epithelial characteristics. In addition to the prostate, hyperplasias and squamous metaplasias were detected in epithelia of the epididymis, vas deferens, coagulating gland, preputial gland and salivary gland. However, and in contrast to a recent study, no lesions reminiscent of highgrade prostate intraepithelial neoplasia were detected. Since b-catenin was activated in several cell types and impinged upon the viability of these mice, it was not possible to evaluate the cumulative effect over more than 3 months. To assess long-term consequences of b-catenin activation, mutant and control prostate tissues were transplanted into the mammary fat pads of wild-type males. Notably, squamous metaplasias, intra-acinous hyperplasia and possible neoplastic transformation were observed after a total of 18 weeks of b-catenin stimulation. This suggests that the transdifferentiation into squamous metaplasias is an early response of endodermderived cells to b-catenin, and that the development of intra-acinous hyperplasias or neoplastic foci is a later event.

Research paper thumbnail of Mammary Epithelial Cells Are Not Able to Undergo Pregnancy-Dependent Differentiation in the Absence of the Helix-Loop-Helix Inhibitor Id2

Molecular Endocrinology, 2002

Mammary alveolar development during pregnancy is triggered by hormone signals. The prolactin rece... more Mammary alveolar development during pregnancy is triggered by hormone signals. The prolactin receptor/Jak2/signal transducer and activator of transcription (Stat) 5 signal transduction pathway is the principal mediator of these cues and alveolar development is abrogated in its absence. The loss of the basic helix-loop-helix protein inhibitor of differentiation (Id)2 results in a similar defect. To investigate the role of Id2 in mammary epithelium, we performed structural and molecular analyses. Id2-null mammary epithelial cells were unable to form alveoli; the epithelial architecture was disorganized and dissimilar from early stages of alveologenesis in wild-type glands. The epithelial cells retained the ductal marker Na-K-Cl cotransporter (NKCC)1. Nuclear localization of Stat5a and downregulation of NKCC1 was observed in some areas, indicating a limited response to pregnancy signals. The differentiation status of Id2-null tissue at term was further characterized with cDNA microarrays enriched in mammary specific sequences (mammochip). Some of the early differentiation markers for mammary epithelium were expressed in the Id2-null tissue, whereas genes that are expressed at later stages of pregnancy were not induced. From these results, we conclude that, in the absence of Id2, mammary epithelial development is arrested at an early stage of pregnancy. (Molecular

Research paper thumbnail of Di- and Tri- but Not Monomethylation on Histone H3 Lysine 36 Marks Active Transcription of Genes Involved in Flowering Time Regulation and Other Processes in Arabidopsis thaliana

Molecular and Cellular Biology, 2008

Histone lysines can be mono-, di-or tri-methylated, providing an ample magnitude of epigenetic in... more Histone lysines can be mono-, di-or tri-methylated, providing an ample magnitude of epigenetic information for transcription regulation. In fungi, SET2 is the sole methyltransferase responsible for mono-, di-and tri-methylation of H3K36. Here we show that in Arabidopsis the degree of H3K36 methylation is regulated by distinct methyltransferases. The SET2-homologs SDG8 and SDG26 each can methylate oligonucleosomes in vitro and both proteins are localized in the nucleus. While the previously reported loss-of-function sdg8 mutants have an early-flowering phenotype, the loss-of-function sdg26 mutants show a late-flowering phenotype. Consistently, several MADS-box flowering repressors are down-regulated by sdg8 but up-regulated by sdg26. The sdg8 but not the sdg26 mutant plants show a dramatically reduced level of both di-and tri-methyl-H3K36 and an increased level of mono-methyl-H3K36. SDG8 is thus specifically required for di-and tri-methylation of H3K36. Our results further establish that H3K36 di-and tri-but not mono-methylation correlates with transcription activation. Finally, we show that SDG8 and VIP4, which encodes a component of the PAF1 complex, act independently and synergistically in transcription regulation. Together our results reveal that the deposition of H3K36 methylation is finely regulated, possibly to cope with the complex regulation of growth and development in higher eukaryotes.

Research paper thumbnail of Genomic approach to study floral development genes in Rosa sp

PloS one, 2011

Cultivated for centuries, the varieties of rose have been selected based on a number of flower tr... more Cultivated for centuries, the varieties of rose have been selected based on a number of flower traits. Understanding the genetic and molecular basis that contributes to these traits will impact on future improvements for this economically important ornamental plant. In this study, we used scanning electron microscopy and sections of meristems and flowers to establish a precise morphological calendar from early rose flower development stages to senescing flowers. Global gene expression was investigated from floral meristem initiation up to flower senescence in three rose genotypes exhibiting contrasted floral traits including continuous versus once flowering and simple versus double flower architecture, using a newly developed Affymetrix microarray (Rosa1_Affyarray) tool containing sequences representing 4765 unigenes expressed during flower development. Data analyses permitted the identification of genes associated with floral transition, floral organs initiation up to flower senesc...

Research paper thumbnail of Misregulation of AUXIN RESPONSE FACTOR 8 underlies the developmental abnormalities caused by three distinct viral silencing suppressors in Arabidopsis

PLoS pathogens, 2011

In Arabidopsis, micro (mi)RNAs and trans-acting (ta-si)RNAs synthesized directly or indirectly th... more In Arabidopsis, micro (mi)RNAs and trans-acting (ta-si)RNAs synthesized directly or indirectly through the DICER-LIKE-1 (DCL1) ribonuclease have roles in patterning and hormonal responses, while DCL2,3,4-dependent small-interfering (si)RNAs are mainly involved in silencing of transposable elements and antiviral defense. Viral suppressors of RNA silencing (VSRs) produced by phytoviruses to counter plant defense may perturb plant developmental programs because of the collision of their inhibitory effects with the regulatory action of endogenous miRNAs and ta-siRNAs. This could explain the similar developmental aberrations displayed by Arabidopsis miRNA/ta-siRNA pathway mutants, including dcl1, and by some VSR-expressing plants. Nonetheless, the molecular bases for these morphological aberrations have remained mysterious, and their contribution to viral disease symptoms/virulence unexplored. The extent of VSR inhibitory actions to other types of endogenous small RNAs remains also uncle...

Research paper thumbnail of Genome-wide interacting effects of sucrose and herbicide-mediated stress in Arabidopsis thaliana: novel insights into atrazine toxicity and sucrose-induced tolerance

BMC Genomics, 2007

Background: Soluble sugars, which play a central role in plant structure and metabolism, are also... more Background: Soluble sugars, which play a central role in plant structure and metabolism, are also involved in the responses to a number of stresses, and act as metabolite signalling molecules that activate specific or hormone-crosstalk transduction pathways. The different roles of exogenous sucrose in the tolerance of Arabidopsis thaliana plantlets to the herbicide atrazine and oxidative stress were studied by a transcriptomic approach using CATMA arrays.

Research paper thumbnail of Analysis of CATMA transcriptome data identifies hundreds of novel functional genes and improves gene models in the Arabidopsis genome

BMC Genomics, 2007

Since the finishing of the sequencing of the Arabidopsis thaliana genome, the Arabidopsis communi... more Since the finishing of the sequencing of the Arabidopsis thaliana genome, the Arabidopsis community and the annotator centers have been working on the improvement of gene annotation at the structural and functional levels. In this context, we have used the large CATMA resource on the Arabidopsis transcriptome to search for genes missed by different annotation processes. Probes on the CATMA microarrays are specific gene sequence tags (GSTs) based on the CDS models predicted by the Eugene software. Among the 24 576 CATMA v2 GSTs, 677 are in regions considered as intergenic by the TAIR annotation. We analyzed the cognate transcriptome data in the CATMA resource and carried out data-mining to characterize novel genes and improve gene models.

Research paper thumbnail of Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

BMC Genomics, 2010

Background: The physiological function of the prion protein remains largely elusive while its key... more Background: The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results: Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions: These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.

Research paper thumbnail of Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated β-catenin

Oncogene, 2003

β-Catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletio... more β-Catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletion of exon 3 from the endogenous β-catenin gene in differentiating mammary alveolar epithelium of the mouse results in the generation of an activated protein that lacks amino acids 5–80. This is accompanied by a loss of mammary epithelial differentiation and a transdifferentiation process to

Research paper thumbnail of Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated beta-catenin

Oncogene, Jan 17, 2003

Beta-catenin is an executor of Wnt signaling and it can control cell fate and specification. Dele... more Beta-catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletion of exon 3 from the endogenous beta-catenin gene in differentiating mammary alveolar epithelium of the mouse results in the generation of an activated protein that lacks amino acids 5-80. This is accompanied by a loss of mammary epithelial differentiation and a transdifferentiation process to squamous metaplasias. To further understand the molecular process of transdifferentiation, the expression of genes in mammary tissue was profiled in the absence and presence of activated of beta-catenin. Microarrays were generated that carry about 8500 cDNA clones with approximately 6000 obtained from mammary tissue. Mutant tissues, which had undergone either partial (TD1) or complete (TD2) squamous transdifferentiation, were compared with wild-type mammary tissue. Four groups of genes were identified. Group 1 contained genes whose expression was induced in both mutant tissues. Groups 2 and 3 co...

Research paper thumbnail of Genome-scale Arabidopsis promoter array identifies targets of the histone acetyltransferase GCN5

The Plant Journal, 2008

We have assembled approximately 20 000 Arabidopsis thaliana promoter regions, compatible with fun... more We have assembled approximately 20 000 Arabidopsis thaliana promoter regions, compatible with functional studies that require cloning and with microarray applications. The promoter fragments can be captured as modular entry clones (MultiSite Gateway format) via site-specific recombinational cloning, and transferred into vectors of choice to investigate transcriptional networks. The fragments can also be amplified by PCR and printed on glass arrays. In combination with immunoprecipitation of protein-DNA complexes (ChIP-chip), these arrays enable characterization of binding sites for chromatin-associated proteins or the extent of chromatin modifications at genome scale. The Arabidopsis histone acetyltransferase GCN5 associated with 40% of the tested promoters. At most sites, binding did not depend on the integrity of the GCN5 bromodomain. However, the presence of the bromodomain was necessary for binding to 11% of the promoter regions, and correlated with acetylation of lysine 14 of histone H3 in these promoters. Combined analysis of ChIP-chip and transcriptomic data indicated that binding of GCN5 does not strictly correlate with gene activation. GCN5 has previously been shown to be required for light-regulated gene expression and growth, and we found that GCN5 targets were enriched in early light-responsive genes. Thus, in addition to its transcriptional activation function, GCN5 may play an important role in priming activation of inducible genes under non-induced conditions.

Research paper thumbnail of hca: an Arabidopsis mutant exhibiting unusual cambial activity and altered vascular patterning

The Plant Journal, 2005

By screening a T-DNA population of Arabidopsis mutants for alterations in inflorescence stem vasc... more By screening a T-DNA population of Arabidopsis mutants for alterations in inflorescence stem vasculature, we have isolated a mutant with a dramatic increase in vascular tissue development, characterized by a continuous ring of xylem/phloem. This phenotype is the consequence of premature and numerous cambial cell divisions in both the fascicular and interfascicular regions that result in the loss of the alternate vascular bundle/fiber organization typically observed in Arabidopsis stems. The mutant was therefore designated high cambial activity (hca). The hca mutation also resulted in pleiotropic effects including stunting and a delay in developmental events such as flowering and senescence. The physiological characterization of hca seedlings in vitro revealed an altered auxin and cytokinin response and, most strikingly, an enhanced sensitivity to cytokinin. These results were substantiated by comparative microarray analysis between hca and wild-type plants. The genetic analysis of hca indicated that the mutant phenotype was not tagged by the T-DNA and that the hca mutation segregated as a single recessive locus, mapping to the long arm of chromosome 4. We propose that hca is involved in mechanisms controlling the arrangement of vascular bundles throughout the plant by regulating the auxin-cytokinin sensitivity of vascular cambial cells. Thus, the hca mutant is a useful model for examining the genetic and hormonal control of cambial growth and differentiation.

Research paper thumbnail of Cross-talk between ethylene and drought signalling pathways is mediated by the sunflower Hahb-4 transcription factor

The Plant Journal, 2006

Hahb-4 is a member of the Helianthus annuus (sunflower) subfamily I of HD-Zip proteins that is tr... more Hahb-4 is a member of the Helianthus annuus (sunflower) subfamily I of HD-Zip proteins that is transcriptionally regulated by water availability and abscisic acid. Transgenic Arabidopsis thaliana plants overexpressing this transcription factor (TF) exhibit a characteristic phenotype that includes a strong tolerance to water stress. Here we show that this TF is a new component of ethylene signalling pathways, and that it induces a marked delay in senescence. Plants overexpressing Hahb-4 are less sensitive to external ethylene, enter the senescence pathway later and do not show the typical triple response. Furthermore, transgenic plants expressing this gene under the control of its own inducible promoter showed an inverse correlation between ethylene sensitivity and Hahb-4 levels. Potential targets of Hahb-4 were identified by comparing the transcriptome of Hahb-4-transformed and wild-type plants using microarrays and quantitative RT-PCR. Expression of this TF has a major repressive effect on genes related to ethylene synthesis, such as ACO and SAM, and on genes related to ethylene signalling, such as ERF2 and ERF5. Expression studies in sunflower indicate that Hahb-4 transcript levels are elevated in mature/senescent leaves. Expression of Hahb-4 is induced by ethylene, concomitantly with several genes homologous to the targets identified in the transcriptome analysis (HA-ACOa and HA-ACOb). Transient transformation of sunflower leaves demonstrated the action of Hahb-4 in the regulation of ethylene-related genes. We propose that Hahb-4 is involved in a novel conserved mechanism related to ethylene-mediated senescence that functions to improve desiccation tolerance.

Research paper thumbnail of Walls are thin 1 (WAT1), an Arabidopsis homolog of Medicago truncatula NODULIN21, is a tonoplast-localized protein required for secondary wall formation in fibers

The Plant Journal, 2010

By combining Zinnia elegans in vitro tracheary element genomics with reverse genetics in Arabidop... more By combining Zinnia elegans in vitro tracheary element genomics with reverse genetics in Arabidopsis, we have identified a new upstream component of secondary wall formation in xylary and interfascicular fibers. Walls are thin 1 (WAT1), an Arabidopsis thaliana homolog of Medicago truncatula NODULIN 21 (MtN21), encodes a plant-specific, predicted integral membrane protein, and is a member of the plant drug/metabolite exporter (P-DME) family (transporter classification number: TC 2.A.7.3). Although WAT1 is ubiquitously expressed throughout the plant, its expression is preferentially associated with vascular tissues, including developing xylem vessels and fibers. WAT1:GFP fusion protein analysis demonstrated that WAT1 is localized to the tonoplast. Analysis of wat1 mutants revealed two cell wall-related phenotypes in stems: a defect in cell elongation, resulting in a dwarfed habit and little to no secondary cell walls in fibers. Secondary walls of vessel elements were unaffected by the mutation. The secondary wall phenotype was supported by comparative transcriptomic and metabolomic analyses of wat1 and wild-type stems, as many transcripts and metabolites involved in secondary wall formation were reduced in abundance. Unexpectedly, these experiments also revealed a modification in tryptophan (Trp) and auxin metabolism that might contribute to the wat1 phenotype. Together, our data demonstrate an essential role for the WAT1 tonoplast protein in the control of secondary cell wall formation in fibers.

Research paper thumbnail of Arabidopsis NRP1 and NRP2 Encode Histone Chaperones and Are Required for Maintaining Postembryonic Root Growth

THE PLANT CELL ONLINE, 2006

NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) is conserved from yeast to human and was proposed to act as a... more NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) is conserved from yeast to human and was proposed to act as a histone chaperone. While budding yeast contains a single NAP1 gene, multicellular organisms, including plants and animals, contain several NAP1 and NAP1-RELATED PROTEIN (NRP) genes. However, the biological role of these genes has been largely unexamined. Here, we show that, in Arabidopsis thaliana, simultaneous knockout of the two NRP genes, NRP1 and NRP2, impaired postembryonic root growth. In the nrp1-1 nrp2-1 double mutant, arrest of cell cycle progression at G2/M and disordered cellular organization occurred in root tips. The mutant seedlings exhibit perturbed expression of ;100 genes, including some genes involved in root proliferation and patterning. The mutant plants are highly sensitive to genotoxic stress and show increased levels of DNA damage and the release of transcriptional gene silencing. NRP1 and NRP2 are localized in the nucleus and can form homomeric and heteromeric protein complexes. Both proteins specifically bind histones H2A and H2B and associate with chromatin in vivo. We propose that NRP1 and NRP2 act as H2A/H2B chaperones in the maintenance of dynamic chromatin in epigenetic inheritance. 65643603 or 33-3-88614442.

Research paper thumbnail of Polycomb Repressive Complex 2 Controls the Embryo-to-Seedling Phase Transition

PLoS Genetics, 2011

Polycomb repressive complex 2 (PRC2) is a key regulator of epigenetic states catalyzing histone H... more Polycomb repressive complex 2 (PRC2) is a key regulator of epigenetic states catalyzing histone H3 lysine 27 trimethylation (H3K27me3), a repressive chromatin mark. PRC2 composition is conserved from humans to plants, but the function of PRC2 during the early stage of plant life is unclear beyond the fact that it is required for the development of endosperm, a nutritive tissue that supports embryo growth. Circumventing the requirement of PRC2 in endosperm allowed us to generate viable homozygous null mutants for FERTILIZATION INDEPENDENT ENDOSPERM (FIE), which is the single Arabidopsis homolog of Extra Sex Combs, an indispensable component of Drosophila and mammalian PRC2. Here we show that H3K27me3 deposition is abolished genome-wide in fie mutants demonstrating the essential function of PRC2 in placing this mark in plants as in animals. In contrast to animals, we find that PRC2 function is not required for initial body plan formation in Arabidopsis. Rather, our results show that fie mutant seeds exhibit enhanced dormancy and germination defects, indicating a deficiency in terminating the embryonic phase. After germination, fie mutant seedlings switch to generative development that is not sustained, giving rise to neoplastic, callus-like structures. Further genome-wide studies showed that only a fraction of PRC2 targets are transcriptionally activated in fie seedlings and that this activation is accompanied in only a few cases with deposition of H3K4me3, a mark associated with gene activity and considered to act antagonistically to H3K27me3. Up-regulated PRC2 target genes were found to act at different hierarchical levels from transcriptional master regulators to a wide range of downstream targets. Collectively, our findings demonstrate that PRC2-mediated regulation represents a robust system controlling developmental phase transitions, not only from vegetative phase to flowering but also especially from embryonic phase to the seedling stage.

Research paper thumbnail of An Integrated Genomics Approach to Define Niche Establishment by Rhodococcus fascians

PLANT PHYSIOLOGY, 2009

Chlorophyll fluorescence parameters were measured with an Imaging-PAM Chlorophyll Fluorometer (Wa... more Chlorophyll fluorescence parameters were measured with an Imaging-PAM Chlorophyll Fluorometer (Walz). Mock-inoculated controls and R. fascians-infected plants (strains D188 and D188-5) were compared in their photosynthetic capacity at 4, 7, 14, and 21 dpi. At least 15 areas of interest, over Niche Establishment by Rhodococcus fascians

Research paper thumbnail of The Cold-Induced Early Activation of Phospholipase C and D Pathways Determines the Response of Two Distinct Clusters of Genes in Arabidopsis Cell Suspensions

PLANT PHYSIOLOGY, 2005

In plants, a temperature downshift represents a major stress that will lead to the induction or r... more In plants, a temperature downshift represents a major stress that will lead to the induction or repression of many genes. Therefore, the cold signal has to be perceived and transmitted to the nucleus. In response to a cold exposure, we have shown that the phospholipase D (PLD) and the phospholipase C (PLC)/diacylglycerol kinase pathways are simultaneously activated. The role of these pathways in the cold response has been investigated by analyzing the transcriptome of cold-treated Arabidopsis (Arabidopsis thaliana) suspension cells in the presence of U73122 or ethanol, inhibitors of the PLC/diacylglycerol kinase pathway and of the phosphatidic acid produced by PLD, respectively. This approach showed that the expression of many genes was modified by the cold response in the presence of such agents. The cold responses of most of the genes were repressed, thus correlating with the inhibitory effect of U73122 or ethanol. We were thus able to identify 58 genes that were regulated by temperature downshift via PLC activity and 87 genes regulated by temperature downshift via PLD-produced phosphatidic acid. Interestingly, each inhibitor appeared to affect different cold response genes. These results support the idea that both the PLC and PLD pathways are upstream of two different signaling pathways that lead to the activation of the cold response. The connection of these pathways with the CBF pathway, currently the most understood genetic system playing a role in cold acclimation, is discussed. ).

Research paper thumbnail of Genetic Variation Suggests Interaction between Cold Acclimation and Metabolic Regulation of Leaf Senescence

PLANT PHYSIOLOGY, 2006

The extent to which leaf senescence is induced by nitrogen deficiency or by sugar accumulation va... more The extent to which leaf senescence is induced by nitrogen deficiency or by sugar accumulation varies between natural accessions of Arabidopsis (Arabidopsis thaliana). Analysis of senescence in plants of the Bay-0 3 Shahdara recombinant inbred line (RIL) population revealed a large variation in developmental senescence of the whole leaf rosette, which was in agreement with the extent to which glucose (Glc) induced senescence in the different lines. To determine the regulatory basis of genetic differences in the Glc response, we investigated changes in gene expression using Complete Arabidopsis Transcriptome MicroArray (CATMA) analysis. Genes whose regulation did not depend on the genetic background, as well as genes whose regulation was specific to individual RILs, were identified. In RIL 310, a line that does not show the typical senescence response to Glc, stress response genes, especially those responding to cold stress, were induced by Glc. We therefore tested whether cold acclimation delays senescence by reducing sugar sensitivity. In cold-acclimated plants, leaf senescence was severely delayed and Glc did not induce the typical senescence response. Together, our results suggest that cold acclimation extends rosette longevity by affecting metabolic regulation of senescence, thereby allowing vernalization-dependent plants to survive the winter period. The role of functional chloroplasts and of nitrogen and phosphate availability in this regulation is discussed.

Research paper thumbnail of Phosphatidylinositol 4-Kinase Activation Is an Early Response to Salicylic Acid in Arabidopsis Suspension Cells

PLANT PHYSIOLOGY, 2007

J.-P.R., L.T.); and Institute of Experimental Botany, v.v.i., Academy of Sciences of the Czech Re... more J.-P.R., L.T.); and Institute of Experimental Botany, v.v.i., Academy of Sciences of the Czech Republic, Prague 165 02, Czech Republic (L.B.)

Research paper thumbnail of Activation of β-catenin in prostate epithelium induces hyperplasias and squamous transdifferentiation

Oncogene, 2003

The Wnt/b-catenin signaling pathway is critical for normal mammalian development, the specificati... more The Wnt/b-catenin signaling pathway is critical for normal mammalian development, the specification of epidermal cells and neoplastic transformation of intestinal epithelium. However, precise molecular information regarding cell-specific responses to b-catenin signaling has been limited. This question was addressed using a mouse model in which exon 3 of the b-catenin gene was deleted in several cell types with loxP-mediated recombination utilizing a Cre transgene under control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). The stabilization of b-catenin in prostate epithelium resulted in hyperplasias and extensive transdifferentiation into epidermal-like structures, which expressed keratins 1 and 6, filaggrin, loricrin and involucrin. The cell-specific loss of NKCC1 protein and reduced nuclear Stat5a is further suggestive of a loss of prostate epithelial characteristics. In addition to the prostate, hyperplasias and squamous metaplasias were detected in epithelia of the epididymis, vas deferens, coagulating gland, preputial gland and salivary gland. However, and in contrast to a recent study, no lesions reminiscent of highgrade prostate intraepithelial neoplasia were detected. Since b-catenin was activated in several cell types and impinged upon the viability of these mice, it was not possible to evaluate the cumulative effect over more than 3 months. To assess long-term consequences of b-catenin activation, mutant and control prostate tissues were transplanted into the mammary fat pads of wild-type males. Notably, squamous metaplasias, intra-acinous hyperplasia and possible neoplastic transformation were observed after a total of 18 weeks of b-catenin stimulation. This suggests that the transdifferentiation into squamous metaplasias is an early response of endodermderived cells to b-catenin, and that the development of intra-acinous hyperplasias or neoplastic foci is a later event.

Research paper thumbnail of Mammary Epithelial Cells Are Not Able to Undergo Pregnancy-Dependent Differentiation in the Absence of the Helix-Loop-Helix Inhibitor Id2

Molecular Endocrinology, 2002

Mammary alveolar development during pregnancy is triggered by hormone signals. The prolactin rece... more Mammary alveolar development during pregnancy is triggered by hormone signals. The prolactin receptor/Jak2/signal transducer and activator of transcription (Stat) 5 signal transduction pathway is the principal mediator of these cues and alveolar development is abrogated in its absence. The loss of the basic helix-loop-helix protein inhibitor of differentiation (Id)2 results in a similar defect. To investigate the role of Id2 in mammary epithelium, we performed structural and molecular analyses. Id2-null mammary epithelial cells were unable to form alveoli; the epithelial architecture was disorganized and dissimilar from early stages of alveologenesis in wild-type glands. The epithelial cells retained the ductal marker Na-K-Cl cotransporter (NKCC)1. Nuclear localization of Stat5a and downregulation of NKCC1 was observed in some areas, indicating a limited response to pregnancy signals. The differentiation status of Id2-null tissue at term was further characterized with cDNA microarrays enriched in mammary specific sequences (mammochip). Some of the early differentiation markers for mammary epithelium were expressed in the Id2-null tissue, whereas genes that are expressed at later stages of pregnancy were not induced. From these results, we conclude that, in the absence of Id2, mammary epithelial development is arrested at an early stage of pregnancy. (Molecular

Research paper thumbnail of Di- and Tri- but Not Monomethylation on Histone H3 Lysine 36 Marks Active Transcription of Genes Involved in Flowering Time Regulation and Other Processes in Arabidopsis thaliana

Molecular and Cellular Biology, 2008

Histone lysines can be mono-, di-or tri-methylated, providing an ample magnitude of epigenetic in... more Histone lysines can be mono-, di-or tri-methylated, providing an ample magnitude of epigenetic information for transcription regulation. In fungi, SET2 is the sole methyltransferase responsible for mono-, di-and tri-methylation of H3K36. Here we show that in Arabidopsis the degree of H3K36 methylation is regulated by distinct methyltransferases. The SET2-homologs SDG8 and SDG26 each can methylate oligonucleosomes in vitro and both proteins are localized in the nucleus. While the previously reported loss-of-function sdg8 mutants have an early-flowering phenotype, the loss-of-function sdg26 mutants show a late-flowering phenotype. Consistently, several MADS-box flowering repressors are down-regulated by sdg8 but up-regulated by sdg26. The sdg8 but not the sdg26 mutant plants show a dramatically reduced level of both di-and tri-methyl-H3K36 and an increased level of mono-methyl-H3K36. SDG8 is thus specifically required for di-and tri-methylation of H3K36. Our results further establish that H3K36 di-and tri-but not mono-methylation correlates with transcription activation. Finally, we show that SDG8 and VIP4, which encodes a component of the PAF1 complex, act independently and synergistically in transcription regulation. Together our results reveal that the deposition of H3K36 methylation is finely regulated, possibly to cope with the complex regulation of growth and development in higher eukaryotes.

Research paper thumbnail of Genomic approach to study floral development genes in Rosa sp

PloS one, 2011

Cultivated for centuries, the varieties of rose have been selected based on a number of flower tr... more Cultivated for centuries, the varieties of rose have been selected based on a number of flower traits. Understanding the genetic and molecular basis that contributes to these traits will impact on future improvements for this economically important ornamental plant. In this study, we used scanning electron microscopy and sections of meristems and flowers to establish a precise morphological calendar from early rose flower development stages to senescing flowers. Global gene expression was investigated from floral meristem initiation up to flower senescence in three rose genotypes exhibiting contrasted floral traits including continuous versus once flowering and simple versus double flower architecture, using a newly developed Affymetrix microarray (Rosa1_Affyarray) tool containing sequences representing 4765 unigenes expressed during flower development. Data analyses permitted the identification of genes associated with floral transition, floral organs initiation up to flower senesc...

Research paper thumbnail of Misregulation of AUXIN RESPONSE FACTOR 8 underlies the developmental abnormalities caused by three distinct viral silencing suppressors in Arabidopsis

PLoS pathogens, 2011

In Arabidopsis, micro (mi)RNAs and trans-acting (ta-si)RNAs synthesized directly or indirectly th... more In Arabidopsis, micro (mi)RNAs and trans-acting (ta-si)RNAs synthesized directly or indirectly through the DICER-LIKE-1 (DCL1) ribonuclease have roles in patterning and hormonal responses, while DCL2,3,4-dependent small-interfering (si)RNAs are mainly involved in silencing of transposable elements and antiviral defense. Viral suppressors of RNA silencing (VSRs) produced by phytoviruses to counter plant defense may perturb plant developmental programs because of the collision of their inhibitory effects with the regulatory action of endogenous miRNAs and ta-siRNAs. This could explain the similar developmental aberrations displayed by Arabidopsis miRNA/ta-siRNA pathway mutants, including dcl1, and by some VSR-expressing plants. Nonetheless, the molecular bases for these morphological aberrations have remained mysterious, and their contribution to viral disease symptoms/virulence unexplored. The extent of VSR inhibitory actions to other types of endogenous small RNAs remains also uncle...

Research paper thumbnail of Genome-wide interacting effects of sucrose and herbicide-mediated stress in Arabidopsis thaliana: novel insights into atrazine toxicity and sucrose-induced tolerance

BMC Genomics, 2007

Background: Soluble sugars, which play a central role in plant structure and metabolism, are also... more Background: Soluble sugars, which play a central role in plant structure and metabolism, are also involved in the responses to a number of stresses, and act as metabolite signalling molecules that activate specific or hormone-crosstalk transduction pathways. The different roles of exogenous sucrose in the tolerance of Arabidopsis thaliana plantlets to the herbicide atrazine and oxidative stress were studied by a transcriptomic approach using CATMA arrays.

Research paper thumbnail of Analysis of CATMA transcriptome data identifies hundreds of novel functional genes and improves gene models in the Arabidopsis genome

BMC Genomics, 2007

Since the finishing of the sequencing of the Arabidopsis thaliana genome, the Arabidopsis communi... more Since the finishing of the sequencing of the Arabidopsis thaliana genome, the Arabidopsis community and the annotator centers have been working on the improvement of gene annotation at the structural and functional levels. In this context, we have used the large CATMA resource on the Arabidopsis transcriptome to search for genes missed by different annotation processes. Probes on the CATMA microarrays are specific gene sequence tags (GSTs) based on the CDS models predicted by the Eugene software. Among the 24 576 CATMA v2 GSTs, 677 are in regions considered as intergenic by the TAIR annotation. We analyzed the cognate transcriptome data in the CATMA resource and carried out data-mining to characterize novel genes and improve gene models.

Research paper thumbnail of Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

BMC Genomics, 2010

Background: The physiological function of the prion protein remains largely elusive while its key... more Background: The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results: Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions: These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.