C. Desplan - Academia.edu (original) (raw)
Papers by C. Desplan
European Journal of Biochemistry, 1985
In view of the possible physiological importance of the 9-kDa cholecalcin (a 9000-Mr cholecalcife... more In view of the possible physiological importance of the 9-kDa cholecalcin (a 9000-Mr cholecalciferol-induced calcium-binding protein) in the intestinal transport of calcium in mammals, the gene expression of this protein has been analysed. Its regulation in the digestive tract of the growing rat by calcitriol (1,25-dihydroxycholecalciferol) was studied using a specific cloned [32P]cDNA to 9-kDa cholecalcin. Northern hybridisation studies show that the cDNA sequence hybridises to a single 500-600-nucleotide species throughout the digestive tract and therefore demonstrate identical 9-kDa-cholecalcin mRNA processing in the whole of the intestine and caecum. The highest concentrations of cholecalcin mRNA occur in the duodenum, proximal jejunum and caecum. The observed differences in 9-kDa-cholecalcin mRNA levels correlate well with both the in vivo variations in cholecalcin itself and with the known intestinal sites of calcium absorption. The whole intestine is able to respond to exogenous calcitriol but the response of the distal intestine and caecum, as measured by the increase in cholecalcin mRNA and corresponding protein, was proportionally higher than in the duodenum. The rapid production of fully functional cholecalcin mRNA, which was detectable as early as 1 h after a single dose of calcitriol to vitamin-D-deficient rats, provides convincing evidence that calcitriol increases 9-kDa cholecalcin production by increasing cholecalcin gene expression at the transcriptional level.
Journal of Histochemistry & Cytochemistry, 1986
We have previously described the molecular cloning of a cDNA fragment synthesized from rat duoden... more We have previously described the molecular cloning of a cDNA fragment synthesized from rat duodenal mRNA coding for a 9000-dalton vitamin D-induced calcium-binding protein (9-kDa CaBP) (3). We now report the use of this cloned cDNA to study the cytological distribution of 9-kDa CaBP mRNA in rat duodenum by in situ hybridization. Tissue sections, fixed in ethanol:acetic acid, were hybridized to the 3H-cDNA probe and processed for autoradiography. The specificity of the CaBP mRNA-DNA hybrid formation was checked using 3H-labeled plasmid pBR322 DNA as a control probe. 9k-Da CaBP mRNA, visualized by silver grains, was found only in the absorptive epithelial cells, and the concentration was greater in the cells at the villous tips than in those of the crypts. The 9k-Da CaBP mRNA was observed mainly in the cytoplasm of the columnar cells and less frequently in the nucleus. Labeling was not seen in the brush border and goblet cells. The submucosa, with Brunner's glands and muscularis, ...
FEBS Letters, 1983
The primary step of calcitonin biosynthesis was studied in a normal organ: chicken ultimobranchia... more The primary step of calcitonin biosynthesis was studied in a normal organ: chicken ultimobranchial gland, a tissue particularly rich in calcitonin secretory cells. Poly(A)-rich RNA was extracted and purified from ultimobranchial organs and translated in a reticulocyte lysate in the presence of labelled methionine. Polyacrylamide gel electrophoresis of specific immunoprecipitates revealed a major band of M, 14500 and a band of ik& 13300. Thus, in chicken the precursor of calcitonin is a M, 14500 polypeptide. The minor component of I% 13300 could represent limited processing by the reticulocyte lysate.
FEBS Letters, 1985
DNA complementary to chlcken ultlmobranchlal gland mRNA was cloned mto the Pst I site of plasmrd ... more DNA complementary to chlcken ultlmobranchlal gland mRNA was cloned mto the Pst I site of plasmrd vector pBR322 A plasmid was selected by DNA-mRNA hybrrdization We report here the partral nucleotide sequence of chlcken calcltomn mRNA and the deduced complete ammo acid sequence of chlcken cahtomn mRNA Calcltonin Chtcken ultrmobranchtal gland CD NA clonmg Nucleotlde sequence Ammo acid sequence
Experimental Biology and Medicine, 1978
ABSTRACT
Development, 2000
The Torso signal transduction pathway exhibits two opposite effects on the activity of the Bicoid... more The Torso signal transduction pathway exhibits two opposite effects on the activity of the Bicoid (Bcd) morphogen: (i) Bcd function is repressed by Torso (Tor) at the anterior pole of the embryo leading to a retraction of the expression of many Bcd targets from the most anterior region of the embryo, where the Tor tyrosine kinase receptor is activated, and (ii) Bcd function is strengthened by Tor in a broader anterior region, as indicated by a shift of the posterior border of Bcd targets towards the anterior pole in embryos deprived from Tor activity. Anterior repression of Bcd targets was not observed in embryos lacking maternal contribution of D-sor, which acts downstream of Tor and encodes a MAP-kinase kinase. This indicates that the Ras signalling cascade is directly involved in this process, although the known transcriptional effectors of the Tor pathway, tll and hkb, are not (Ronchi, E., Treisman, J., Dostatni, N., Struhl, G. and Desplan, C. (1993) Cell 74, 347-355). Bcd is a ...
Development, 2000
In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis whil... more In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis while the ends of the embryo are patterned by the maternal terminal system. At the posterior pole, expression of terminal gap genes is mediated by the local activation of the Torso receptor tyrosine kinase (Tor). At the anterior, terminal gap genes are also activated by the Tor pathway but Bcd contributes to their activation. Here we present evidence that Tor and Bcd act independently on common target genes in an additive manner. Furthermore, we show that the terminal maternal system is not required for proper head development, since high levels of Bcd activity can functionally rescue the lack of terminal system activity at the anterior pole. This observation is consistent with a recent evolution of an anterior morphogenetic center consisting of Bcd and anterior Tor function.
Development, 1997
The Drosophila gap-like segmentation genes orthodenticle, empty spiracles and buttonhead (btd) ar... more The Drosophila gap-like segmentation genes orthodenticle, empty spiracles and buttonhead (btd) are expressed and required in overlapping domains in the head region of the blastoderm stage embryo. Their expression domains correspond to two or three segment anlagen that fail to develop in each mutant. It has been proposed that these overlapping expression domains mediate head metamerization and could generate a combinatorial code to specify segment identity. To test this model, we developed a system for targeted gene expression in the early embryo, based on region specific promoters and the flp-out system. Misex-pression of btd in the anterior half of the blastoderm embryo directed by the hunchback proximal promoter rescues the btd mutant head phenotype to wild-type. This indicates that, while btd activity is required for the formation of specific head segments, its ectopic expression does not disturb head development. We conclude that the spatial limits of btd expression are not inst...
Molecular and Cellular Biology, 1989
The engrailed (en) gene functions throughout Drosophila development and is expressed in a success... more The engrailed (en) gene functions throughout Drosophila development and is expressed in a succession of intricate spatial patterns as development proceeds. Normal en function relies on an extremely large cis-acting regulatory region (70 kilobases). We are using evolutionary conservation to help identify en sequences important in regulating patterned expression. Sequence comparison of 2.6 kilobases upstream of the en coding region of D. melanogaster and D. virilis (estimated divergence time, 60 million years) showed that 30% of this DNA occurs in islands of near perfect sequence conservation. One of these conserved islands contains binding sites for homeodomain-containing proteins. It has been shown genetically that homeodomain-containing proteins regulate en expression. Our data suggested that this regulation may be direct. The remaining conserved islands may contain binding sites for other regulatory proteins.
Cold Spring Harbor protocols, 2011
The Drosophila visual system is composed of the retina and the optic lobes, which are the ganglia... more The Drosophila visual system is composed of the retina and the optic lobes, which are the ganglia where photoreceptors project and initial processing of visual inputs occur. This protocol outlines procedures for dissecting the optic lobes from Drosophila larvae, pupae, and adults. It also describes methods for visualizing the anatomy of brain neural circuits by staining with fluorescent secondary antibodies and primary antibodies specific for various neuronal populations and architectural features. MATERIALS RECIPES: Please see the end of this article for recipes indicated by . It is essential that you consult the appropriate Material Safety Data Sheets and your institution's Environmental Health and Safety Office for proper handling of equipment and hazardous materials used in this protocol. Reagents CO 2 (for anesthetizing adult fiies) Drosophila at stage of interest Glycerol (50%) Normal goat serum (Lampire Biological Laboratories) (5%, v/v in PBST) Aliquot in very small volumes and store at −20°C. Paraformaldehyde (16%) (Electron Microscopy Sciences) PBST (PBS containing 0.3% Triton X-100) Phosphate-buffered saline (PBS) (1×, pH 7.4) Primary antibodies (see Table 1) Secondary antibodies (see Table 2) Vectashield mounting medium (for preserving fluorescence) (Vector Laboratories) Equipment Cover glasses (18 × 18-mm and 24 × 50-mm) (Fisher Scientific) Dissecting microscope Dissection dishes (three-well, glass) (Fisher Scientific
Proceedings of the European Dialysis and Transplant Association. European Dialysis and Transplant Association, 1979
Nine uraemic patients not yet on dialysis received IV 1 microgram/kg/min of propranolol for 85 mi... more Nine uraemic patients not yet on dialysis received IV 1 microgram/kg/min of propranolol for 85 min after a priming dose of 1 mg. Fifteen days later six of them received IV 1.2 microgram/kg/min of metoprolol after a priming dose of 1.2 mg. Plasma concentrations of PTH and calcitonin decreased significantly with propranolol but not with metoprolol. No change was observed with either drug as regards plasma concentration of total and ionised Ca and PO4. Heart rate was decreased similarly with both drugs. We conclude that (i) propranolol acutely suppresses PTH and Calcitonin secretion in uraemic patients. This warrants further studies to assess its long term effects on the secretion of these hormones and on renal osteodystrophy; (ii) the contrast between the significant effect of propranolol and the lack of effect with metoprolol supports the concept that PTH and CT secretion are moderated through specific beta 2 receptors.
Neuron, 2015
Temporal sequences of transcription factors (tTFs) in Drosophila neural progenitors generate neur... more Temporal sequences of transcription factors (tTFs) in Drosophila neural progenitors generate neuronal diversity. Mattar et al. (2015) identify Casz1/Castor as a late temporal identity factor in mouse retinal progenitors that is regulated by the early factor Ikzf1/Hunchback, thus generalizing the notion of tTFs.
Developmental Cell, 2013
Neuroepithelial cell proliferation must be carefully balanced with the transition to neuroblast (... more Neuroepithelial cell proliferation must be carefully balanced with the transition to neuroblast (neural stem cell) to control neurogenesis. Here, we show that loss of the Drosophila microRNA mir-8 (the homolog of vertebrate miR-200 family) results in both excess proliferation and ectopic neuroblast transition. Unexpectedly, mir-8 is expressed in a subpopulation of optic-lobe-associated cortex glia that extend processes that ensheath the neuroepithelium, suggesting that glia cells communicate with the neuroepithelium. We provide evidence that miR-8-positive glia express Spitz, a transforming growth factor a (TGF-a)-like ligand that triggers epidermal growth factor receptor (EGFR) activation to promote neuroepithelial proliferation and neuroblast formation. Further, our experiments suggest that miR-8 ensures both a correct glial architecture and the spatiotemporal control of Spitz protein synthesis via direct binding to Spitz 3 0 UTR. Together, these results establish glial-derived cues as key regulatory elements in the control of neuroepithelial cell proliferation and the neuroblast transition.
European Journal of Biochemistry, 1985
In view of the possible physiological importance of the 9-kDa cholecalcin (a 9000-Mr cholecalcife... more In view of the possible physiological importance of the 9-kDa cholecalcin (a 9000-Mr cholecalciferol-induced calcium-binding protein) in the intestinal transport of calcium in mammals, the gene expression of this protein has been analysed. Its regulation in the digestive tract of the growing rat by calcitriol (1,25-dihydroxycholecalciferol) was studied using a specific cloned [32P]cDNA to 9-kDa cholecalcin. Northern hybridisation studies show that the cDNA sequence hybridises to a single 500-600-nucleotide species throughout the digestive tract and therefore demonstrate identical 9-kDa-cholecalcin mRNA processing in the whole of the intestine and caecum. The highest concentrations of cholecalcin mRNA occur in the duodenum, proximal jejunum and caecum. The observed differences in 9-kDa-cholecalcin mRNA levels correlate well with both the in vivo variations in cholecalcin itself and with the known intestinal sites of calcium absorption. The whole intestine is able to respond to exogenous calcitriol but the response of the distal intestine and caecum, as measured by the increase in cholecalcin mRNA and corresponding protein, was proportionally higher than in the duodenum. The rapid production of fully functional cholecalcin mRNA, which was detectable as early as 1 h after a single dose of calcitriol to vitamin-D-deficient rats, provides convincing evidence that calcitriol increases 9-kDa cholecalcin production by increasing cholecalcin gene expression at the transcriptional level.
Journal of Histochemistry & Cytochemistry, 1986
We have previously described the molecular cloning of a cDNA fragment synthesized from rat duoden... more We have previously described the molecular cloning of a cDNA fragment synthesized from rat duodenal mRNA coding for a 9000-dalton vitamin D-induced calcium-binding protein (9-kDa CaBP) (3). We now report the use of this cloned cDNA to study the cytological distribution of 9-kDa CaBP mRNA in rat duodenum by in situ hybridization. Tissue sections, fixed in ethanol:acetic acid, were hybridized to the 3H-cDNA probe and processed for autoradiography. The specificity of the CaBP mRNA-DNA hybrid formation was checked using 3H-labeled plasmid pBR322 DNA as a control probe. 9k-Da CaBP mRNA, visualized by silver grains, was found only in the absorptive epithelial cells, and the concentration was greater in the cells at the villous tips than in those of the crypts. The 9k-Da CaBP mRNA was observed mainly in the cytoplasm of the columnar cells and less frequently in the nucleus. Labeling was not seen in the brush border and goblet cells. The submucosa, with Brunner's glands and muscularis, ...
FEBS Letters, 1983
The primary step of calcitonin biosynthesis was studied in a normal organ: chicken ultimobranchia... more The primary step of calcitonin biosynthesis was studied in a normal organ: chicken ultimobranchial gland, a tissue particularly rich in calcitonin secretory cells. Poly(A)-rich RNA was extracted and purified from ultimobranchial organs and translated in a reticulocyte lysate in the presence of labelled methionine. Polyacrylamide gel electrophoresis of specific immunoprecipitates revealed a major band of M, 14500 and a band of ik& 13300. Thus, in chicken the precursor of calcitonin is a M, 14500 polypeptide. The minor component of I% 13300 could represent limited processing by the reticulocyte lysate.
FEBS Letters, 1985
DNA complementary to chlcken ultlmobranchlal gland mRNA was cloned mto the Pst I site of plasmrd ... more DNA complementary to chlcken ultlmobranchlal gland mRNA was cloned mto the Pst I site of plasmrd vector pBR322 A plasmid was selected by DNA-mRNA hybrrdization We report here the partral nucleotide sequence of chlcken calcltomn mRNA and the deduced complete ammo acid sequence of chlcken cahtomn mRNA Calcltonin Chtcken ultrmobranchtal gland CD NA clonmg Nucleotlde sequence Ammo acid sequence
Experimental Biology and Medicine, 1978
ABSTRACT
Development, 2000
The Torso signal transduction pathway exhibits two opposite effects on the activity of the Bicoid... more The Torso signal transduction pathway exhibits two opposite effects on the activity of the Bicoid (Bcd) morphogen: (i) Bcd function is repressed by Torso (Tor) at the anterior pole of the embryo leading to a retraction of the expression of many Bcd targets from the most anterior region of the embryo, where the Tor tyrosine kinase receptor is activated, and (ii) Bcd function is strengthened by Tor in a broader anterior region, as indicated by a shift of the posterior border of Bcd targets towards the anterior pole in embryos deprived from Tor activity. Anterior repression of Bcd targets was not observed in embryos lacking maternal contribution of D-sor, which acts downstream of Tor and encodes a MAP-kinase kinase. This indicates that the Ras signalling cascade is directly involved in this process, although the known transcriptional effectors of the Tor pathway, tll and hkb, are not (Ronchi, E., Treisman, J., Dostatni, N., Struhl, G. and Desplan, C. (1993) Cell 74, 347-355). Bcd is a ...
Development, 2000
In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis whil... more In Drosophila, the gradient of the Bicoid (Bcd) morphogen organizes the anteroposterior axis while the ends of the embryo are patterned by the maternal terminal system. At the posterior pole, expression of terminal gap genes is mediated by the local activation of the Torso receptor tyrosine kinase (Tor). At the anterior, terminal gap genes are also activated by the Tor pathway but Bcd contributes to their activation. Here we present evidence that Tor and Bcd act independently on common target genes in an additive manner. Furthermore, we show that the terminal maternal system is not required for proper head development, since high levels of Bcd activity can functionally rescue the lack of terminal system activity at the anterior pole. This observation is consistent with a recent evolution of an anterior morphogenetic center consisting of Bcd and anterior Tor function.
Development, 1997
The Drosophila gap-like segmentation genes orthodenticle, empty spiracles and buttonhead (btd) ar... more The Drosophila gap-like segmentation genes orthodenticle, empty spiracles and buttonhead (btd) are expressed and required in overlapping domains in the head region of the blastoderm stage embryo. Their expression domains correspond to two or three segment anlagen that fail to develop in each mutant. It has been proposed that these overlapping expression domains mediate head metamerization and could generate a combinatorial code to specify segment identity. To test this model, we developed a system for targeted gene expression in the early embryo, based on region specific promoters and the flp-out system. Misex-pression of btd in the anterior half of the blastoderm embryo directed by the hunchback proximal promoter rescues the btd mutant head phenotype to wild-type. This indicates that, while btd activity is required for the formation of specific head segments, its ectopic expression does not disturb head development. We conclude that the spatial limits of btd expression are not inst...
Molecular and Cellular Biology, 1989
The engrailed (en) gene functions throughout Drosophila development and is expressed in a success... more The engrailed (en) gene functions throughout Drosophila development and is expressed in a succession of intricate spatial patterns as development proceeds. Normal en function relies on an extremely large cis-acting regulatory region (70 kilobases). We are using evolutionary conservation to help identify en sequences important in regulating patterned expression. Sequence comparison of 2.6 kilobases upstream of the en coding region of D. melanogaster and D. virilis (estimated divergence time, 60 million years) showed that 30% of this DNA occurs in islands of near perfect sequence conservation. One of these conserved islands contains binding sites for homeodomain-containing proteins. It has been shown genetically that homeodomain-containing proteins regulate en expression. Our data suggested that this regulation may be direct. The remaining conserved islands may contain binding sites for other regulatory proteins.
Cold Spring Harbor protocols, 2011
The Drosophila visual system is composed of the retina and the optic lobes, which are the ganglia... more The Drosophila visual system is composed of the retina and the optic lobes, which are the ganglia where photoreceptors project and initial processing of visual inputs occur. This protocol outlines procedures for dissecting the optic lobes from Drosophila larvae, pupae, and adults. It also describes methods for visualizing the anatomy of brain neural circuits by staining with fluorescent secondary antibodies and primary antibodies specific for various neuronal populations and architectural features. MATERIALS RECIPES: Please see the end of this article for recipes indicated by . It is essential that you consult the appropriate Material Safety Data Sheets and your institution's Environmental Health and Safety Office for proper handling of equipment and hazardous materials used in this protocol. Reagents CO 2 (for anesthetizing adult fiies) Drosophila at stage of interest Glycerol (50%) Normal goat serum (Lampire Biological Laboratories) (5%, v/v in PBST) Aliquot in very small volumes and store at −20°C. Paraformaldehyde (16%) (Electron Microscopy Sciences) PBST (PBS containing 0.3% Triton X-100) Phosphate-buffered saline (PBS) (1×, pH 7.4) Primary antibodies (see Table 1) Secondary antibodies (see Table 2) Vectashield mounting medium (for preserving fluorescence) (Vector Laboratories) Equipment Cover glasses (18 × 18-mm and 24 × 50-mm) (Fisher Scientific) Dissecting microscope Dissection dishes (three-well, glass) (Fisher Scientific
Proceedings of the European Dialysis and Transplant Association. European Dialysis and Transplant Association, 1979
Nine uraemic patients not yet on dialysis received IV 1 microgram/kg/min of propranolol for 85 mi... more Nine uraemic patients not yet on dialysis received IV 1 microgram/kg/min of propranolol for 85 min after a priming dose of 1 mg. Fifteen days later six of them received IV 1.2 microgram/kg/min of metoprolol after a priming dose of 1.2 mg. Plasma concentrations of PTH and calcitonin decreased significantly with propranolol but not with metoprolol. No change was observed with either drug as regards plasma concentration of total and ionised Ca and PO4. Heart rate was decreased similarly with both drugs. We conclude that (i) propranolol acutely suppresses PTH and Calcitonin secretion in uraemic patients. This warrants further studies to assess its long term effects on the secretion of these hormones and on renal osteodystrophy; (ii) the contrast between the significant effect of propranolol and the lack of effect with metoprolol supports the concept that PTH and CT secretion are moderated through specific beta 2 receptors.
Neuron, 2015
Temporal sequences of transcription factors (tTFs) in Drosophila neural progenitors generate neur... more Temporal sequences of transcription factors (tTFs) in Drosophila neural progenitors generate neuronal diversity. Mattar et al. (2015) identify Casz1/Castor as a late temporal identity factor in mouse retinal progenitors that is regulated by the early factor Ikzf1/Hunchback, thus generalizing the notion of tTFs.
Developmental Cell, 2013
Neuroepithelial cell proliferation must be carefully balanced with the transition to neuroblast (... more Neuroepithelial cell proliferation must be carefully balanced with the transition to neuroblast (neural stem cell) to control neurogenesis. Here, we show that loss of the Drosophila microRNA mir-8 (the homolog of vertebrate miR-200 family) results in both excess proliferation and ectopic neuroblast transition. Unexpectedly, mir-8 is expressed in a subpopulation of optic-lobe-associated cortex glia that extend processes that ensheath the neuroepithelium, suggesting that glia cells communicate with the neuroepithelium. We provide evidence that miR-8-positive glia express Spitz, a transforming growth factor a (TGF-a)-like ligand that triggers epidermal growth factor receptor (EGFR) activation to promote neuroepithelial proliferation and neuroblast formation. Further, our experiments suggest that miR-8 ensures both a correct glial architecture and the spatiotemporal control of Spitz protein synthesis via direct binding to Spitz 3 0 UTR. Together, these results establish glial-derived cues as key regulatory elements in the control of neuroepithelial cell proliferation and the neuroblast transition.