Claude Desplan - Academia.edu (original) (raw)

Papers by Claude Desplan

Research paper thumbnail of Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features

Cell, Jan 9, 2018

Transcription factors regulate the molecular, morphological, and physiological characteristics of... more Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. We validated and annotated many clusters using RNA sequencing of FACS-sorted single-cell types and cluster-specific genes. To identify transcription factors responsible for inducing specific terminal differentiation features, we generated a "random forest" model, and we showed that the transcription factors Apterous and Traffic-jam are required in many but not all cholinergic and glutamatergic neurons, respectively. In fact, the same terminal characters often can be regulated by different transcription factors in diffe...

Research paper thumbnail of Generation and Evolution of Neural Cell Types and Circuits: Insights from the Drosophila Visual System

Annual review of genetics, Jan 27, 2017

The Drosophila visual system has become a premier model for probing how neural diversity is gener... more The Drosophila visual system has become a premier model for probing how neural diversity is generated during development. Recent work has provided deeper insight into the elaborate mechanisms that control the range of types and numbers of neurons produced, which neurons survive, and how they interact. These processes drive visual function and behavioral preferences. Other studies are beginning to provide insight into how neuronal diversity evolved in insects by adding new cell types and modifying neural circuits. Some of the most powerful comparisons have been those made to the Drosophila visual system, where a deeper understanding of molecular mechanisms allows for the generation of hypotheses about the evolution of neural anatomy and function. The evolution of new neural types contributes additional complexity to the brain and poses intriguing questions about how new neurons interact with existing circuitry. We explore how such individual changes in a variety of species might play...

Research paper thumbnail of The evolutionary diversity of insect retinal mosaics: common design principles and emerging molecular logic

Trends in genetics : TIG, 2015

Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Baup... more Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Bauplan or ancestral structure, similar developmental strategies are used. For instance, different classes of photoreceptor cells (PRs) are distributed stochastically and/or localized in different regions of the retina. Here, we focus on recent progress made towards understanding the molecular principles behind patterning retinal mosaics of insects, one of the most diverse groups of animals adapted to life on land, in the air, under water, or on the water surface. Morphological, physiological, and behavioral studies from many species provide detailed descriptions of the vast variation in retinal design and function. By integrating this knowledge with recent progress in the characterization of insect Rhodopsins as well as insight from the model organism Drosophila melanogaster, we seek to identify the molecular logic behind the adaptation of retinal mosaics to the habitat and way of life of a...

Research paper thumbnail of Patterning the Drosophila retina for detection of color and polarized light

Research paper thumbnail of Conserved miR-8/miR-200 Defines a Glial Niche that Controls Neuroepithelial Expansion and Neuroblast Transition

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.

Research paper thumbnail of So many pieces, one puzzle: cell type specification and visual circuitry in flies and mice

Genes & development, 2014

The visual system is a powerful model for probing the development, connectivity, and function of ... more The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering fields of research: (1) understanding how the fates of different cell types are specified during development, (2) revealing the synaptic connections between identified cell types ("connectomics") by high-resolution three-dimensional circuit anatomy, and (3) causal testing of how identified circuit elements contribute to visual perception and behavior. Here we discuss representative examples from fly and mouse models to illustrate the ongoing success of this tripartite strategy, focusing on the ways it is enhancing our understanding of visual processing and other sensory systems.

Research paper thumbnail of Building a projection map for photoreceptor neurons in the Drosophila optic lobes

Seminars in Cell & Developmental Biology, 2004

The sensory tasks performed by the eye are diverse and complex. In Drosophila, the eye performs m... more The sensory tasks performed by the eye are diverse and complex. In Drosophila, the eye performs motion detection for navigation as well as detection of the quality of light (color and polarized light). Both types of inputs are processed separately, as different photoreceptors are specialized in these tasks and contact different target cell layers in the optic lobe. However, their respective outputs are likely to be integrated in higher brain centers. Here, we discuss the cell diversity and potential role of the several ganglia that form the fly optic lobe. We also discuss the power of modern genetic tools to provide the potential to trace the visual neural networks.

Research paper thumbnail of Extraction of Functional Binding Sites from Unique Regulatory Regions: The Drosophila Early Developmental Enhancers

Genome Research, 2002

The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticat... more The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticated regulatory systems in higher eukaryotes. An elaborate code in their DNA sequence translates both maternal and early embryonic regulatory signals into spatial distribution of transcription factors. One of the most striking features of this code is the redundancy of binding sites for these transcription factors (BSTF). Using this redundancy, we explored the possibility of predicting functional binding sites in a single enhancer region without any prior consensus/matrix description or evolutionary sequence comparisons. We developed a conceptually simple algorithm,Scanseq, that employs an original statistical evaluation for identifying the most redundant motifs and locates the position of potential BSTF in a given regulatory region. To estimate the biological relevance of our predictions, we built thorough literature-based annotations for the best-known Drosophiladevelopmental enhancers a...

Research paper thumbnail of New section titled Evolution of Developmental Control Mechanisms

Developmental Biology, 2008

Research paper thumbnail of Two Pax genes, eye gone and eyeless, act cooperatively in promoting Drosophila eye development

Development, 2003

We report the identification of a Drosophila Pax gene, eye gone (eyg), which is required for eye ... more We report the identification of a Drosophila Pax gene, eye gone (eyg), which is required for eye development. Loss-of-function eyg mutations cause reduction or absence of the eye. Similar to the Pax6 eyeless (ey) gene, ectopic expression of eyg induces extra eye formation, but at sites different from those induced by ey. Several lines of evidence suggest that eygand ey act cooperatively: (1) eyg expression is not regulated by ey, nor does it regulate ey expression, (2) eyg-induced ectopic morphogenetic furrow formation does not require ey, nor does ey-induced ectopic eye production require eyg, (3) eyg and ey can partially substitute for the function of the other, and (4) coexpression of eyg and ey has a synergistic enhancement of ectopic eye formation. Our results also show that eyg has two major functions: to promote cell proliferation in the eye disc and to promote eye development through suppression of wg transcription.

Research paper thumbnail of Homothorax and Extradenticle alter the transcription factor network in Drosophila ommatidia at the dorsal rim of the retina

Development, 2014

A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim... more A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim area (DRA) act as detectors for polarized light. The transcription factor Homothorax (Hth) is expressed in DRA inner photoreceptors R7 and R8 and is both necessary and sufficient to induce the DRA fate, including specialized morphology and unique Rhodopsin expression. Hth expression is the result of Wingless (Wg) pathway activity at the eye margins and restriction to the dorsal eye by the selector genes of the Iroquois complex (Iro-C). However, how the DRA is limited to exactly one or two ommatidial rows is not known. Although several factors regulating the Drosophila retinal mosaic are expressed in DRA ommatidia, the role of Hth in this transcriptional network is uncharacterized. Here we show that Hth functions together with its co-factor Extradenticle (Exd) to repress the R8-specific factor Senseless (Sens) in DRA R8 cells, allowing expression of an ultraviolet-sensitive R7 Rhodopsin ...

Research paper thumbnail of Homothorax and Extradenticle alter the transcription factor network in Drosophila ommatidia at the dorsal rim of the retina

Development, 2014

A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim... more A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim area (DRA) act as detectors for polarized light. The transcription factor Homothorax (Hth) is expressed in DRA inner photoreceptors R7 and R8 and is both necessary and sufficient to induce the DRA fate, including specialized morphology and unique Rhodopsin expression. Hth expression is the result of Wingless (Wg) pathway activity at the eye margins and restriction to the dorsal eye by the selector genes of the Iroquois complex (Iro-C). However, how the DRA is limited to exactly one or two ommatidial rows is not known. Although several factors regulating the Drosophila retinal mosaic are expressed in DRA ommatidia, the role of Hth in this transcriptional network is uncharacterized. Here we show that Hth functions together with its co-factor Extradenticle (Exd) to repress the R8-specific factor Senseless (Sens) in DRA R8 cells, allowing expression of an ultraviolet-sensitive R7 Rhodopsin ...

Research paper thumbnail of Opposite feedbacks in the Hippo pathway for growth control and neural fate

Introduction: A fi nite number of signaling pathways are repurposed during animal development to ... more Introduction: A fi nite number of signaling pathways are repurposed during animal development to regulate an extraordinary array of cellular decisions. Elucidating context-specifi c mechanisms is crucial for understanding how cellular diversity is generated and for defi ning potential avenues of pathway mis-regulation during disease. The Hippo tumor suppressor pathway has been primarily studied in growth control where it inhibits the oncogenic transcriptional coactivator Yorkie (Yki) (YAP/TAZ in vertebrates).

Research paper thumbnail of A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate expression with Rh3 in R7 cells

Development, 1997

The photoreceptor cells of the Drosophila compound eye are precisely organized in elementary unit... more The photoreceptor cells of the Drosophila compound eye are precisely organized in elementary units called ommatidia. The outer (R1-R6) and inner (R7, R8) photoreceptors represent two physiologically distinct systems with two different projection targets in the brain (for review see Hardie, 1985). All cells of the primary system, R1-R6, express the same rhodopsin and are functionally identical. In contrast, the R7 and R8 photoreceptors are different from each other. They occupy anatomically precise positions, with R7 on top of R8. In fact, there are several classes of R7/R8 pairs, which differ morphologically and functionally and are characterized by the expression of one of two R7-specific opsins, rh3 or rh4. Here, we describe the identification of a new opsin gene, rhodopsin 5, expressed in one subclass of R8 cells. Interestingly, this subclass represents R8 cells that are directly underneath the R7 photoreceptors expressing rh3, but are never under those expressing rh4. These resu...

Research paper thumbnail of A functional homologue of goosecoid in Drosophila

Development, 1996

We have cloned a Drosophila homologue (D-gsc) of the vertebrate homeobox gene goosecoid (gsc). In... more We have cloned a Drosophila homologue (D-gsc) of the vertebrate homeobox gene goosecoid (gsc). In the Gsc proteins, the pressure for conservation has been imposed on the homeodomain, the functional domain of the protein: sequence homology is limited to the homeodomain (78% identity) and to a short stretch of 7 aminoacids also found in other homeoproteins such as Engrailed. Despite this weak homology, D-gsc is able to mimic gsc function in a Xenopus assay, as shown by its ability to rescue the axis development of a UV-irradiated embryo. Moreover, our data suggest that the position of insect and vertebrate gsc homologues within a regulatory network has also been conserved: D-gsc expression is controlled by decapentaplegic, orthodenticle, sloppy-paired and tailless whose homologues control gsc expression (for BMP4 and Otx-2), or are expressed at the right time and the right place (for XFKH1/Pintallavis and Tlx) to be interacting with gsc during vertebrate development. However, the patt...

Research paper thumbnail of A new visualization approach for identifying mutations that affect differentiation and organization of the Drosophila ommatidia

Development, 2001

The Drosophila eye is widely used as a model system to study neuronal differentiation, survival a... more The Drosophila eye is widely used as a model system to study neuronal differentiation, survival and axon projection. Photoreceptor differentiation starts with the specification of a founder cell R8, which sequentially recruits other photoreceptor neurons to the ommatidium. The eight photoreceptors that compose each ommatidium exist in two chiral forms organized along two axes of symmetry and this pattern represents a paradigm to study tissue polarity. We have developed a method of fluoroscopy to visualize the different types of photoreceptors and the organization of the ommatidia in living animals. This allowed us to perform an F(1) genetic screen to isolate mutants affecting photoreceptor differentiation, survival or planar polarity. We illustrate the power of this detection system using known genetic backgrounds and new mutations that affect ommatidial differentiation, morphology or chirality.

Research paper thumbnail of High bicoid levels render the terminal system dispensable for Drosophila head development

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.

Research paper thumbnail of Drosophila Goosecoid requires a conserved heptapeptide for repression of paired-class homeoprotein activators

Development, 1998

Goosecoid (Gsc) is a homeodomain protein expressed in the organizer region of vertebrate embryos.... more Goosecoid (Gsc) is a homeodomain protein expressed in the organizer region of vertebrate embryos. Its Drosophila homologue, D-Gsc, has been implicated in the formation of the Stomatogastric Nervous System. Although there are no apparent similarities between the phenotypes of mutations in the gsc gene in flies and mice, all known Gsc proteins can rescue dorsoanterior structures in ventralized Xenopus embryos. We describe how D-Gsc behaves as a transcriptional repressor in Drosophila cells, acting through specific palindromic HD binding sites (P3K). D-Gsc is a 'passive repressor' of activator homeoproteins binding to the same sites and an 'active repressor' of activators binding to distinct sites. In addition, D-Gsc is able to strongly repress transcription activated by Paired-class homeoproteins through P3K, via specific protein-protein interactions in what we define as 'interactive repression'. This form of repression requires the short conserved GEH/eh-1 dom...

Research paper thumbnail of A green¯uorescent protein enhancer trap screen in Drosophila photoreceptor cells

The Drosophila ommatidia contain two classes of photoreceptor cells (PR's), the outer and th... more The Drosophila ommatidia contain two classes of photoreceptor cells (PR's), the outer and the inner PR's. We performed an enhancer trap screen in order to target genes speci®cally expressed in PR's. Using the UAS/GAL4 method with enhanced green¯uorescent protein (eGFP) as a vital marker, we screened 180 000¯ies. Out of 2730 lines exhibiting new eGFP patterns, we focused on 16 lines expressing eGFP in particular subsets of PR's. In particular, we describe three lines inserted near the spalt major, m-spondin and furrowed genes, whose respective expression patterns resemble those genes. These genes had not been reported to be expressed in the adult eye. These examples clearly show the ability of our screen to target genes expressed in the adult Drosophila eye. q

Research paper thumbnail of De-evolution' of Drosophila toward a more generic mode of axis patterning

The genetics of the establishment of the primary axes of the early embryo have been worked out in... more The genetics of the establishment of the primary axes of the early embryo have been worked out in great detail Drosophila. However, evidence has accumulated that Drosophila employs a mode of patterning that is not shared with most insects. In particular, the use of the morphogenic gradient of the Bicoid homeoprotein appears to be a novel addition to the fly developmental toolkit. To better understand the ancestral mode of patterning that is probably more widely used by insects, several groups have used Evo-Devo approaches as well as sophisticated genetic manipulations of Drosophila to achieve some form of 'de-evolution' of this derived insect. Genetic manipulations of the beetle Tribolium and the wasp Nasonia have validated most of these results.

Research paper thumbnail of Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features

Cell, Jan 9, 2018

Transcription factors regulate the molecular, morphological, and physiological characteristics of... more Transcription factors regulate the molecular, morphological, and physiological characteristics of neurons and generate their impressive cell-type diversity. To gain insight into the general principles that govern how transcription factors regulate cell-type diversity, we used large-scale single-cell RNA sequencing to characterize the extensive cellular diversity in the Drosophila optic lobes. We sequenced 55,000 single cells and assigned them to 52 clusters. We validated and annotated many clusters using RNA sequencing of FACS-sorted single-cell types and cluster-specific genes. To identify transcription factors responsible for inducing specific terminal differentiation features, we generated a "random forest" model, and we showed that the transcription factors Apterous and Traffic-jam are required in many but not all cholinergic and glutamatergic neurons, respectively. In fact, the same terminal characters often can be regulated by different transcription factors in diffe...

Research paper thumbnail of Generation and Evolution of Neural Cell Types and Circuits: Insights from the Drosophila Visual System

Annual review of genetics, Jan 27, 2017

The Drosophila visual system has become a premier model for probing how neural diversity is gener... more The Drosophila visual system has become a premier model for probing how neural diversity is generated during development. Recent work has provided deeper insight into the elaborate mechanisms that control the range of types and numbers of neurons produced, which neurons survive, and how they interact. These processes drive visual function and behavioral preferences. Other studies are beginning to provide insight into how neuronal diversity evolved in insects by adding new cell types and modifying neural circuits. Some of the most powerful comparisons have been those made to the Drosophila visual system, where a deeper understanding of molecular mechanisms allows for the generation of hypotheses about the evolution of neural anatomy and function. The evolution of new neural types contributes additional complexity to the brain and poses intriguing questions about how new neurons interact with existing circuitry. We explore how such individual changes in a variety of species might play...

Research paper thumbnail of The evolutionary diversity of insect retinal mosaics: common design principles and emerging molecular logic

Trends in genetics : TIG, 2015

Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Baup... more Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Bauplan or ancestral structure, similar developmental strategies are used. For instance, different classes of photoreceptor cells (PRs) are distributed stochastically and/or localized in different regions of the retina. Here, we focus on recent progress made towards understanding the molecular principles behind patterning retinal mosaics of insects, one of the most diverse groups of animals adapted to life on land, in the air, under water, or on the water surface. Morphological, physiological, and behavioral studies from many species provide detailed descriptions of the vast variation in retinal design and function. By integrating this knowledge with recent progress in the characterization of insect Rhodopsins as well as insight from the model organism Drosophila melanogaster, we seek to identify the molecular logic behind the adaptation of retinal mosaics to the habitat and way of life of a...

Research paper thumbnail of Patterning the Drosophila retina for detection of color and polarized light

Research paper thumbnail of Conserved miR-8/miR-200 Defines a Glial Niche that Controls Neuroepithelial Expansion and Neuroblast Transition

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.

Research paper thumbnail of So many pieces, one puzzle: cell type specification and visual circuitry in flies and mice

Genes & development, 2014

The visual system is a powerful model for probing the development, connectivity, and function of ... more The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering fields of research: (1) understanding how the fates of different cell types are specified during development, (2) revealing the synaptic connections between identified cell types ("connectomics") by high-resolution three-dimensional circuit anatomy, and (3) causal testing of how identified circuit elements contribute to visual perception and behavior. Here we discuss representative examples from fly and mouse models to illustrate the ongoing success of this tripartite strategy, focusing on the ways it is enhancing our understanding of visual processing and other sensory systems.

Research paper thumbnail of Building a projection map for photoreceptor neurons in the Drosophila optic lobes

Seminars in Cell & Developmental Biology, 2004

The sensory tasks performed by the eye are diverse and complex. In Drosophila, the eye performs m... more The sensory tasks performed by the eye are diverse and complex. In Drosophila, the eye performs motion detection for navigation as well as detection of the quality of light (color and polarized light). Both types of inputs are processed separately, as different photoreceptors are specialized in these tasks and contact different target cell layers in the optic lobe. However, their respective outputs are likely to be integrated in higher brain centers. Here, we discuss the cell diversity and potential role of the several ganglia that form the fly optic lobe. We also discuss the power of modern genetic tools to provide the potential to trace the visual neural networks.

Research paper thumbnail of Extraction of Functional Binding Sites from Unique Regulatory Regions: The Drosophila Early Developmental Enhancers

Genome Research, 2002

The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticat... more The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticated regulatory systems in higher eukaryotes. An elaborate code in their DNA sequence translates both maternal and early embryonic regulatory signals into spatial distribution of transcription factors. One of the most striking features of this code is the redundancy of binding sites for these transcription factors (BSTF). Using this redundancy, we explored the possibility of predicting functional binding sites in a single enhancer region without any prior consensus/matrix description or evolutionary sequence comparisons. We developed a conceptually simple algorithm,Scanseq, that employs an original statistical evaluation for identifying the most redundant motifs and locates the position of potential BSTF in a given regulatory region. To estimate the biological relevance of our predictions, we built thorough literature-based annotations for the best-known Drosophiladevelopmental enhancers a...

Research paper thumbnail of New section titled Evolution of Developmental Control Mechanisms

Developmental Biology, 2008

Research paper thumbnail of Two Pax genes, eye gone and eyeless, act cooperatively in promoting Drosophila eye development

Development, 2003

We report the identification of a Drosophila Pax gene, eye gone (eyg), which is required for eye ... more We report the identification of a Drosophila Pax gene, eye gone (eyg), which is required for eye development. Loss-of-function eyg mutations cause reduction or absence of the eye. Similar to the Pax6 eyeless (ey) gene, ectopic expression of eyg induces extra eye formation, but at sites different from those induced by ey. Several lines of evidence suggest that eygand ey act cooperatively: (1) eyg expression is not regulated by ey, nor does it regulate ey expression, (2) eyg-induced ectopic morphogenetic furrow formation does not require ey, nor does ey-induced ectopic eye production require eyg, (3) eyg and ey can partially substitute for the function of the other, and (4) coexpression of eyg and ey has a synergistic enhancement of ectopic eye formation. Our results also show that eyg has two major functions: to promote cell proliferation in the eye disc and to promote eye development through suppression of wg transcription.

Research paper thumbnail of Homothorax and Extradenticle alter the transcription factor network in Drosophila ommatidia at the dorsal rim of the retina

Development, 2014

A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim... more A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim area (DRA) act as detectors for polarized light. The transcription factor Homothorax (Hth) is expressed in DRA inner photoreceptors R7 and R8 and is both necessary and sufficient to induce the DRA fate, including specialized morphology and unique Rhodopsin expression. Hth expression is the result of Wingless (Wg) pathway activity at the eye margins and restriction to the dorsal eye by the selector genes of the Iroquois complex (Iro-C). However, how the DRA is limited to exactly one or two ommatidial rows is not known. Although several factors regulating the Drosophila retinal mosaic are expressed in DRA ommatidia, the role of Hth in this transcriptional network is uncharacterized. Here we show that Hth functions together with its co-factor Extradenticle (Exd) to repress the R8-specific factor Senseless (Sens) in DRA R8 cells, allowing expression of an ultraviolet-sensitive R7 Rhodopsin ...

Research paper thumbnail of Homothorax and Extradenticle alter the transcription factor network in Drosophila ommatidia at the dorsal rim of the retina

Development, 2014

A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim... more A narrow band of ommatidia in the dorsal periphery of the Drosophila retina called the dorsal rim area (DRA) act as detectors for polarized light. The transcription factor Homothorax (Hth) is expressed in DRA inner photoreceptors R7 and R8 and is both necessary and sufficient to induce the DRA fate, including specialized morphology and unique Rhodopsin expression. Hth expression is the result of Wingless (Wg) pathway activity at the eye margins and restriction to the dorsal eye by the selector genes of the Iroquois complex (Iro-C). However, how the DRA is limited to exactly one or two ommatidial rows is not known. Although several factors regulating the Drosophila retinal mosaic are expressed in DRA ommatidia, the role of Hth in this transcriptional network is uncharacterized. Here we show that Hth functions together with its co-factor Extradenticle (Exd) to repress the R8-specific factor Senseless (Sens) in DRA R8 cells, allowing expression of an ultraviolet-sensitive R7 Rhodopsin ...

Research paper thumbnail of Opposite feedbacks in the Hippo pathway for growth control and neural fate

Introduction: A fi nite number of signaling pathways are repurposed during animal development to ... more Introduction: A fi nite number of signaling pathways are repurposed during animal development to regulate an extraordinary array of cellular decisions. Elucidating context-specifi c mechanisms is crucial for understanding how cellular diversity is generated and for defi ning potential avenues of pathway mis-regulation during disease. The Hippo tumor suppressor pathway has been primarily studied in growth control where it inhibits the oncogenic transcriptional coactivator Yorkie (Yki) (YAP/TAZ in vertebrates).

Research paper thumbnail of A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate expression with Rh3 in R7 cells

Development, 1997

The photoreceptor cells of the Drosophila compound eye are precisely organized in elementary unit... more The photoreceptor cells of the Drosophila compound eye are precisely organized in elementary units called ommatidia. The outer (R1-R6) and inner (R7, R8) photoreceptors represent two physiologically distinct systems with two different projection targets in the brain (for review see Hardie, 1985). All cells of the primary system, R1-R6, express the same rhodopsin and are functionally identical. In contrast, the R7 and R8 photoreceptors are different from each other. They occupy anatomically precise positions, with R7 on top of R8. In fact, there are several classes of R7/R8 pairs, which differ morphologically and functionally and are characterized by the expression of one of two R7-specific opsins, rh3 or rh4. Here, we describe the identification of a new opsin gene, rhodopsin 5, expressed in one subclass of R8 cells. Interestingly, this subclass represents R8 cells that are directly underneath the R7 photoreceptors expressing rh3, but are never under those expressing rh4. These resu...

Research paper thumbnail of A functional homologue of goosecoid in Drosophila

Development, 1996

We have cloned a Drosophila homologue (D-gsc) of the vertebrate homeobox gene goosecoid (gsc). In... more We have cloned a Drosophila homologue (D-gsc) of the vertebrate homeobox gene goosecoid (gsc). In the Gsc proteins, the pressure for conservation has been imposed on the homeodomain, the functional domain of the protein: sequence homology is limited to the homeodomain (78% identity) and to a short stretch of 7 aminoacids also found in other homeoproteins such as Engrailed. Despite this weak homology, D-gsc is able to mimic gsc function in a Xenopus assay, as shown by its ability to rescue the axis development of a UV-irradiated embryo. Moreover, our data suggest that the position of insect and vertebrate gsc homologues within a regulatory network has also been conserved: D-gsc expression is controlled by decapentaplegic, orthodenticle, sloppy-paired and tailless whose homologues control gsc expression (for BMP4 and Otx-2), or are expressed at the right time and the right place (for XFKH1/Pintallavis and Tlx) to be interacting with gsc during vertebrate development. However, the patt...

Research paper thumbnail of A new visualization approach for identifying mutations that affect differentiation and organization of the Drosophila ommatidia

Development, 2001

The Drosophila eye is widely used as a model system to study neuronal differentiation, survival a... more The Drosophila eye is widely used as a model system to study neuronal differentiation, survival and axon projection. Photoreceptor differentiation starts with the specification of a founder cell R8, which sequentially recruits other photoreceptor neurons to the ommatidium. The eight photoreceptors that compose each ommatidium exist in two chiral forms organized along two axes of symmetry and this pattern represents a paradigm to study tissue polarity. We have developed a method of fluoroscopy to visualize the different types of photoreceptors and the organization of the ommatidia in living animals. This allowed us to perform an F(1) genetic screen to isolate mutants affecting photoreceptor differentiation, survival or planar polarity. We illustrate the power of this detection system using known genetic backgrounds and new mutations that affect ommatidial differentiation, morphology or chirality.

Research paper thumbnail of High bicoid levels render the terminal system dispensable for Drosophila head development

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.

Research paper thumbnail of Drosophila Goosecoid requires a conserved heptapeptide for repression of paired-class homeoprotein activators

Development, 1998

Goosecoid (Gsc) is a homeodomain protein expressed in the organizer region of vertebrate embryos.... more Goosecoid (Gsc) is a homeodomain protein expressed in the organizer region of vertebrate embryos. Its Drosophila homologue, D-Gsc, has been implicated in the formation of the Stomatogastric Nervous System. Although there are no apparent similarities between the phenotypes of mutations in the gsc gene in flies and mice, all known Gsc proteins can rescue dorsoanterior structures in ventralized Xenopus embryos. We describe how D-Gsc behaves as a transcriptional repressor in Drosophila cells, acting through specific palindromic HD binding sites (P3K). D-Gsc is a 'passive repressor' of activator homeoproteins binding to the same sites and an 'active repressor' of activators binding to distinct sites. In addition, D-Gsc is able to strongly repress transcription activated by Paired-class homeoproteins through P3K, via specific protein-protein interactions in what we define as 'interactive repression'. This form of repression requires the short conserved GEH/eh-1 dom...

Research paper thumbnail of A green¯uorescent protein enhancer trap screen in Drosophila photoreceptor cells

The Drosophila ommatidia contain two classes of photoreceptor cells (PR's), the outer and th... more The Drosophila ommatidia contain two classes of photoreceptor cells (PR's), the outer and the inner PR's. We performed an enhancer trap screen in order to target genes speci®cally expressed in PR's. Using the UAS/GAL4 method with enhanced green¯uorescent protein (eGFP) as a vital marker, we screened 180 000¯ies. Out of 2730 lines exhibiting new eGFP patterns, we focused on 16 lines expressing eGFP in particular subsets of PR's. In particular, we describe three lines inserted near the spalt major, m-spondin and furrowed genes, whose respective expression patterns resemble those genes. These genes had not been reported to be expressed in the adult eye. These examples clearly show the ability of our screen to target genes expressed in the adult Drosophila eye. q

Research paper thumbnail of De-evolution' of Drosophila toward a more generic mode of axis patterning

The genetics of the establishment of the primary axes of the early embryo have been worked out in... more The genetics of the establishment of the primary axes of the early embryo have been worked out in great detail Drosophila. However, evidence has accumulated that Drosophila employs a mode of patterning that is not shared with most insects. In particular, the use of the morphogenic gradient of the Bicoid homeoprotein appears to be a novel addition to the fly developmental toolkit. To better understand the ancestral mode of patterning that is probably more widely used by insects, several groups have used Evo-Devo approaches as well as sophisticated genetic manipulations of Drosophila to achieve some form of 'de-evolution' of this derived insect. Genetic manipulations of the beetle Tribolium and the wasp Nasonia have validated most of these results.