RESUMO
Cell shape remodeling is a principal driver of epithelial tissue morphogenesis. While progress continues to be made in our understanding of the pathways that control the apical (top) geometry of epithelial cells, we know comparatively little about those that control cell basal (bottom) geometry. To examine this, we used the Drosophila ommatidium, which is the basic visual unit of the compound eye. The ommatidium is shaped as a hexagonal prism, and generating this 3D structure requires ommatidial cells to adopt specific apical and basal polygonal geometries. Using this model system, we find that generating cell type-specific basal geometries starts with patterning of the basal extracellular matrix, whereby Laminin accumulates at discrete locations across the basal surface of the retina. We find the Dystroglycan receptor complex (DGC) is required for this patterning by promoting localized Laminin accumulation at the basal surface of cells. Moreover, our results reveal that localized accumulation of Laminin and the DGC are required for directing Integrin adhesion. This induces cell basal geometry remodeling by anchoring the basal surface of cells to the extracellular matrix at specific, Laminin-rich locations. We propose that patterning of a basal extracellular matrix by generating discrete Laminin domains can direct Integrin adhesion to induce cell shape remodeling in epithelial morphogenesis.
Assuntos
Forma Celular , Proteínas de Drosophila , Drosophila melanogaster , Distroglicanas , Matriz Extracelular , Integrinas , Laminina , Retina , Animais , Distroglicanas/metabolismo , Laminina/metabolismo , Integrinas/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Matriz Extracelular/metabolismo , Retina/metabolismo , Retina/crescimento & desenvolvimento , Retina/citologia , Retina/embriologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Morfogênese , Adesão Celular , Drosophila/metabolismo , Drosophila/crescimento & desenvolvimentoRESUMO
Collective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.
Assuntos
Crista Neural , Proteínas Nucleares , Gravidez , Feminino , Humanos , Crista Neural/metabolismo , Proteínas Nucleares/metabolismo , Movimento Celular/fisiologia , QuimiotaxiaRESUMO
Contacts between the endoplasmic reticulum and the plasma membrane (ER-PM contacts) have important roles in membrane lipid and calcium dynamics, yet their organization in polarized epithelial cells has not been thoroughly described. Here we examine ER-PM contacts in hepatocytes in mouse liver using electron microscopy, providing the first comprehensive ultrastructural study of ER-PM contacts in a mammalian epithelial tissue. Our quantitative analyses reveal strikingly distinct ER-PM contact architectures spatially linked to apical, lateral, and basal PM domains. Notably, we find that an extensive network of ER-PM contacts exists at lateral PM domains that form intercellular junctions between hepatocytes. Moreover, the spatial organization of ER-PM contacts is conserved in epithelial spheroids, suggesting that ER-PM contacts may serve conserved roles in epithelial cell architecture. Consistent with this notion, we show that ORP5 activity at ER-PM contacts modulates the apical-basolateral aspect ratio in HepG2 cells. Thus ER-PM contacts have a conserved distribution and crucial roles in PM domain architecture across epithelial cell types.
Assuntos
Cálcio , Retículo Endoplasmático , Animais , Cálcio/metabolismo , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Células Epiteliais/metabolismo , Mamíferos/metabolismo , Lipídeos de Membrana/metabolismo , CamundongosRESUMO
The insect compound eye is the most abundant eye architecture on earth. It comes in a wide variety of shapes and sizes, which are exquisitely adapted to specific ecosystems. Here, we explore the organisational principles and pathways, from molecular to tissular, that underpin the building of this organ and highlight why it is an excellent model system to investigate the relationship between genes and tissue form. The compound eye offers wide fields of view, high sensitivity in motion detection and infinite depth of field. It is made of an array of visual units called ommatidia, which are precisely tiled in 3D to shape the retinal tissue as a dome-like structure. The eye starts off as a 2D epithelium, and it acquires its 3D organisation as ommatidia get into shape. Each ommatidium is made of a complement of retinal cells, including light-detecting photoreceptors and lens-secreting cells. The lens cells generate the typical hexagonal facet lens that lies atop the photoreceptors so that the eye surface consists of a quasi-crystalline array of these hexagonal facet-lenses. This array is curved to various degree, depending on the size and shape of the eye, and on the region of the retina. This curvature sets the resolution and visual field of the eye and is determined by i) the number and size of the facet lens - large ommatidial lenses can be used to generate flat, higher resolution areas, while smaller facets allow for stronger curvature of the eye, and ii) precise control of the inter facet-lens angle, which determines the optical axis of the each ommatidium. In this review we discuss how combinatorial variation in eye primordium shape, ommatidial number, facet lens size and inter facet-lens angle underpins the wide variety of insect eye shapes, and we explore what is known about the mechanisms that might control these parameters.
Assuntos
Ecossistema , Olho , Animais , Insetos , Retina , Visão OcularRESUMO
Movement of epithelial cells in a tissue occurs through neighbor exchange and drives tissue shape changes. It requires intercellular junction remodeling, a process typically powered by the contractile actomyosin cytoskeleton. This has been investigated mainly in homogeneous epithelia, where intercalation takes minutes. However, in some tissues, intercalation involves different cell types and can take hours. Whether slow and fast intercalation share the same mechanisms remains to be examined. To address this issue, we used the fly eye, where the cone cells exchange neighbors over â¼10â h to shape the lens. We uncovered three pathways regulating this slow mode of cell intercalation. First, we found a limited requirement for MyosinII. In this case, mathematical modeling predicts an adhesion-dominant intercalation mechanism. Genetic experiments support this prediction, revealing a role for adhesion through the Nephrin proteins Roughest and Hibris. Second, we found that cone cell intercalation is regulated by the Notch pathway. Third, we show that endocytosis is required for membrane removal and Notch activation. Taken together, our work indicates that adhesion, endocytosis and Notch can direct slow cell intercalation during tissue morphogenesis.
Assuntos
Adesão Celular/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila/embriologia , Endocitose/fisiologia , Receptores Notch/metabolismo , Retina/embriologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Actomiosina/metabolismo , Junções Aderentes/fisiologia , Animais , Padronização Corporal/fisiologia , Moléculas de Adesão Celular Neuronais/metabolismo , Comunicação Celular , Proteínas de Drosophila/genética , Células Epiteliais/citologia , Proteínas do Olho/metabolismo , Adesões Focais/fisiologia , Proteínas de Membrana/metabolismo , Miosina Tipo II/metabolismo , Receptores Notch/genética , Transdução de Sinais/fisiologiaRESUMO
During organogenesis, different cell types need to work together to generate functional multicellular structures. To study this process, we made use of the genetically tractable fly retina, with a focus on the mechanisms that coordinate morphogenesis between the different epithelial cell types that make up the optical lens. Our work shows that these epithelial cells present contractile apical-medial MyosinII meshworks, which control the apical area and junctional geometry of these cells during lens development. Our study also suggests that these MyosinII meshworks drive cell shape changes in response to external forces, and thus they mediate part of the biomechanical coupling that takes place between these cells. Importantly, our work, including mathematical modeling of forces and material stiffness during lens development, raises the possibility that increased cell stiffness acts as a mechanism for limiting this mechanical coupling. We propose this might be required in complex tissues, where different cell types undergo concurrent morphogenesis and where averaging out of forces across cells could compromise individual cell apical geometry and thereby organ function.
Assuntos
Drosophila/crescimento & desenvolvimento , Miosinas/metabolismo , Organogênese , Retina/crescimento & desenvolvimento , Animais , Drosophila/metabolismo , Modelos Biológicos , Miosinas/fisiologia , Retina/metabolismoRESUMO
Cdc42 regulates epithelial morphogenesis together with the Par complex (Baz/Par3-Par6-aPKC), Crumbs (Crb/CRB3) and Stardust (Sdt/PALS1). However, how these proteins work together and interact during epithelial morphogenesis is not well understood. To address this issue, we used the genetically amenable Drosophila pupal photoreceptor and follicular epithelium. We show that during epithelial morphogenesis active Cdc42 accumulates at the developing apical membrane and cell-cell contacts, independently of the Par complex and Crb. However, membrane localization of Baz, Par6-aPKC and Crb all depend on Cdc42. We find that although binding of Cdc42 to Par6 is not essential for the recruitment of Par6 and aPKC to the membrane, it is required for their apical localization and accumulation, which we find also depends on Par6 retention by Crb. In the pupal photoreceptor, membrane recruitment of Par6-aPKC also depends on Baz. Our work shows that Cdc42 is required for this recruitment and suggests that this factor promotes the handover of Par6-aPKC from Baz onto Crb. Altogether, we propose that Cdc42 drives morphogenesis by conferring apical identity, Par-complex assembly and apical accumulation of Crb.
Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Membrana/metabolismo , Células Fotorreceptoras/citologia , Proteína Quinase C/metabolismo , Animais , Polaridade Celular/fisiologia , Drosophila melanogaster/metabolismo , Epitélio/crescimento & desenvolvimento , Morfogênese/fisiologia , Ligação Proteica/fisiologiaRESUMO
Cdc42 - a member of the small Rho GTPase family - regulates cell polarity across organisms from yeast to humans. It is an essential regulator of polarized morphogenesis in epithelial cells, through coordination of apical membrane morphogenesis, lumen formation and junction maturation. In parallel, work in yeast and Caenorhabditiselegans has provided important clues as to how this molecular switch can generate and regulate polarity through localized activation or inhibition, and cytoskeleton regulation. Recent studies have revealed how important and complex these regulations can be during epithelial morphogenesis. This complexity is mirrored by the fact that Cdc42 can exert its function through many effector proteins. In epithelial cells, these include atypical PKC (aPKC, also known as PKC-3), the P21-activated kinase (PAK) family, myotonic dystrophy-related Cdc42 binding kinase beta (MRCKß, also known as CDC42BPB) and neural Wiskott-Aldrich syndrome protein (N-WASp, also known as WASL). Here, we review how the spatial regulation of Cdc42 promotes polarity and polarized morphogenesis of the plasma membrane, with a focus on the epithelial cell type.
Assuntos
Células Epiteliais/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Animais , Células Epiteliais/citologia , Humanos , MorfogêneseRESUMO
Neuronal polarity in the developing cortex begins during the early stages of neural progenitor migration toward the cortical plate and culminates with the specification of the axon and dendrites. Here, we demonstrate that the Ran-dependent nucleocytoplasmic transport machinery is essential for the establishment of cortical neuron polarity. We found that Ran-binding protein 1 (RanBP1) regulates axon specification and dendritic arborization in cultured neurons in vitro and radial neural migration in vivo. During axonogenesis, RanBP1 regulates the cytoplasmic levels of the polarity protein LKB1/Par4, and this is dependent on the nuclear export machinery. Our results show that downstream of RanBP1, LKB1 function is mediated by the STK25-GM130 pathway, which promotes axonogenesis through Golgi regulation. Our results indicate that the nucleocytoplasmic transport machinery is a main regulator of neuron polarity, including radial migration, and that the regulated export of LKB1 through RanBP1 is a limiting step of axonogenesis.
Assuntos
Proteínas de Drosophila/metabolismo , Complexo de Golgi/metabolismo , Neurônios/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Quinases/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Animais , Axônios/metabolismo , Western Blotting , Movimento Celular/fisiologia , Polaridade Celular/genética , Polaridade Celular/fisiologia , Células Cultivadas , Citoplasma/metabolismo , Proteínas de Ligação a DNA/metabolismo , Drosophila , Proteínas de Drosophila/genética , Feminino , Camundongos , Neurônios/citologia , Proteínas Nucleares/genética , Células PC12 , Gravidez , Proteínas Quinases/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Proteína ran de Ligação ao GTP/metabolismoRESUMO
The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM) and zonula adherens (ZA), thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1) gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system.
RESUMO
In Drosophila epithelial cells, apical exclusion of Bazooka (the Drosophila Par3 protein) defines the position of the zonula adherens (ZA), which demarcates the apical and lateral membrane and allows cells to assemble into sheets. Here, we show that the small GTPase Rap1, its effector Canoe (Cno) and the Cdc42 effector kinase Mushroom bodies tiny (Mbt), converge in regulating epithelial morphogenesis by coupling stabilization of the adherens junction (AJ) protein E-Cadherin and Bazooka retention at the ZA. Furthermore, our results show that the localization of Rap1, Cno and Mbt at the ZA is interdependent, indicating that their functions during ZA morphogenesis are interlinked. In this context, we find the Rap1-GEF Dizzy is enriched at the ZA and our results suggest that it promotes Rap1 activity during ZA morphogenesis. Altogether, we propose the Dizzy, Rap1 and Cno pathway and Mbt converge in regulating the interface between Bazooka and AJ material to promote ZA morphogenesis.
Assuntos
Junções Aderentes/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células Fotorreceptoras/metabolismo , Proteínas Quinases/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Junções Aderentes/genética , Animais , Caderinas/genética , Caderinas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Ligação Proteica , Proteínas Quinases/genética , Complexo Shelterina , Proteínas de Ligação a Telômeros/genéticaRESUMO
Polarized epithelia develop distinct cell surface domains, with the apical membrane acquiring characteristic morphological features such as microvilli. Cell polarization is driven by polarity determinants including the evolutionarily conserved partitioning-defective (PAR) proteins that are separated into distinct cortical domains. PAR protein segregation is thought to be a consequence of asymmetric actomyosin contractions. The mechanism of activation of apically polarized actomyosin contractility is unknown. Here we show that the Cdc42 effector MRCK activates myosin-II at the apical pole to segregate aPKC-Par6 from junctional Par3, defining the apical domain. Apically polarized MRCK-activated actomyosin contractility is reinforced by cooperation with aPKC-Par6 downregulating antagonistic RhoA-driven junctional actomyosin contractility, and drives polarization of cytosolic brush border determinants and apical morphogenesis. MRCK-activated polarized actomyosin contractility is required for apical differentiation and morphogenesis in vertebrate epithelia and Drosophila photoreceptors. Our results identify an apical origin of actomyosin-driven morphogenesis that couples cytoskeletal reorganization to PAR polarity signalling.
Assuntos
Membrana Celular/enzimologia , Polaridade Celular , Células Epiteliais/enzimologia , Miotonina Proteína Quinase/metabolismo , Actomiosina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Animais Geneticamente Modificados , Células CACO-2 , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular , Cães , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/enzimologia , Genótipo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Células Madin Darby de Rim Canino , Proteínas de Membrana/metabolismo , Morfogênese , Miosina Tipo II/metabolismo , Miotonina Proteína Quinase/genética , Fenótipo , Células Fotorreceptoras de Invertebrados/enzimologia , Proteína Quinase C/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Proteína cdc42 de Ligação ao GTP/metabolismoRESUMO
The ability of epithelial cells to assemble into sheets relies on their zonula adherens (ZA), a circumferential belt of adherens junction (AJ) material, which can be remodeled during development to shape organs. Here, we show that during ZA remodeling in a model neuroepithelial cell, the Cdc42 effector P21-activated kinase 4 (Pak4/Mbt) regulates AJ morphogenesis and stability through ß-catenin (ß-cat/Arm) phosphorylation. We find that ß-catenin phosphorylation by Mbt, and associated AJ morphogenesis, is needed for the retention of the apical determinant Par3/Bazooka at the remodeling ZA. Importantly, this retention mechanism functions together with Par1-dependent lateral exclusion of Par3/Bazooka to regulate apical membrane differentiation. Our results reveal an important functional link between Pak4, AJ material morphogenesis, and polarity remodeling during organogenesis downstream of Par3.
Assuntos
Junções Aderentes/metabolismo , Polaridade Celular , Olho Composto de Artrópodes/metabolismo , Proteínas de Drosophila/metabolismo , Células Epiteliais/metabolismo , Proteínas Quinases/metabolismo , Junções Aderentes/ultraestrutura , Animais , Diferenciação Celular , Olho Composto de Artrópodes/citologia , Olho Composto de Artrópodes/embriologia , Drosophila/citologia , Drosophila/embriologia , Drosophila/metabolismo , Proteínas de Drosophila/genética , Células Epiteliais/citologia , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Proteínas Quinases/genética , beta Catenina/metabolismoRESUMO
Parallel processing of neuronal inputs relies on assembling neural circuits into distinct synaptic-columns and layers. This is orchestrated by matching recognition molecules between afferent growth cones and target areas. Controlling the expression of these molecules during development is crucial but not well understood. The developing Drosophila visual system is a powerful genetic model for addressing this question. In this model system, the achromatic R1-6 photoreceptors project their axons in the lamina while the R7 and R8 photoreceptors, which are involved in colour detection, project their axons to two distinct synaptic-layers in the medulla. Here we show that the conserved homeodomain transcription factor Orthodenticle (Otd), which in the eye is a main regulator of rhodopsin expression, is also required for R1-6 photoreceptor synaptic-column specific innervation of the lamina. Our data indicate that otd function in these photoreceptors is largely mediated by the recognition molecules flamingo (fmi) and golden goal (gogo). In addition, we find that otd regulates synaptic-layer targeting of R8. We demonstrate that during this process, otd and the R8-specific transcription factor senseless/Gfi1 (sens) function as independent transcriptional inputs that are required for the expression of fmi, gogo and the adhesion molecule capricious (caps), which govern R8 synaptic-layer targeting. Our work therefore demonstrates that otd is a main component of the gene regulatory network that regulates synaptic-column and layer targeting in the fly visual system.
Assuntos
Axônios , Caderinas/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas do Olho/metabolismo , Proteínas de Homeodomínio/metabolismo , Receptores de Superfície Celular/metabolismo , Retina/fisiologia , Animais , Animais Geneticamente Modificados , Caderinas/metabolismo , Drosophila melanogaster , Proteínas do Olho/genética , Redes Reguladoras de Genes , Proteínas de Homeodomínio/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Células Fotorreceptoras de Invertebrados/metabolismo , Receptores de Superfície Celular/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Entry into mitosis is accompanied by profound changes in cortical actomyosin organization. Here, we delineate a pathway downstream of the RhoGEF Pbl/Ect2 that directs this process in a model epithelium. Our data suggest that the release of Pbl/Ect2 from the nucleus at mitotic entry drives Rho-dependent activation of Myosin-II and, in parallel, induces a switch from Arp2/3 to Diaphanous-mediated cortical actin nucleation that depends on Cdc42, aPKC, and Par6. At the same time, the mitotic relocalization of these apical protein complexes to more lateral cell surfaces enables Cdc42/aPKC/Par6 to take on a mitosis-specific function-aiding the assembly of a relatively isotropic metaphase cortex. Together, these data reveal how the repolarization and remodeling of the actomyosin cortex are coordinated upon entry into mitosis to provide cells with the isotropic and rigid form they need to undergo faithful chromosome segregation and division in a crowded tissue environment.
Assuntos
Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Actomiosina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Mitose/fisiologia , Proteína Quinase C/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Western Blotting , Núcleo Celular/metabolismo , Células Cultivadas , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Imunofluorescência , Imunoprecipitação , Ligação ProteicaRESUMO
Understanding how a functional organ can be produced from a small group of cells remains an outstanding question in cell and developmental biology. The developing compound eye of Drosophila has long been a model of choice for addressing this question by dissecting the cellular, genetic and molecular pathways that govern cell specification, differentiation, and multicellular patterning during organogenesis. In this review, the author focussed on cell and tissue morphogenesis during fly retinal development, including the regulated changes in cell shape and cell packing that ultimately determine the shape and architecture of the compound eye. In particular, the author reviewed recent studies that highlight the prominent roles of transcriptional and hormonal controls that orchestrate the cell shape changes, cell-cell junction remodeling and polarized membrane growth that underlie photoreceptor morphogenesis and retinal patterning.
Assuntos
Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento , Retina/embriologia , Transcrição Gênica , Animais , Diferenciação Celular , Drosophila/citologia , Morfogênese , Retina/citologiaRESUMO
The Flower protein family is part of a cell-cell communication pathway that regulates cell competition, in which fit cells eliminate less fit neighbors. A new study demonstrates that this pathway can also govern the culling of unwanted neurons during development.
Assuntos
Canais de Cálcio/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Neurônios/fisiologia , Retina/crescimento & desenvolvimento , AnimaisRESUMO
Cell polarity and cell-cell junctions have pivotal roles in organizing cells into tissues and in mediating cell-cell communication. The transmembrane protein Crumbs has a well-established role in the maintenance of epithelial polarity, and it can also regulate signalling via the Notch and Hippo pathways to influence tissue growth. The functions of Crumbs in epithelial polarity and Hippo-mediated growth depend on its short intracellular domain. Recent evidence now points to a conserved and fundamental role for the extracellular domain of Crumbs in mediating homophilic Crumbs-Crumbs interactions at cell-cell junctions.
Assuntos
Polaridade Celular/fisiologia , Junções Intercelulares/fisiologia , Proteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Animais , Comunicação Celular/fisiologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Humanos , Junções Intercelulares/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismoRESUMO
Morphogenesis of epithelial tissues relies on the interplay between cell division, differentiation and regulated changes in cell shape, intercalation and sorting. These processes are often studied individually in relatively simple epithelia that lack the complexity found during organogenesis when these processes might all coexist simultaneously. To address this issue, we are making use of the developing fly retinal neuroepithelium. Retinal morphogenesis relies on a coordinated sequence of interdependent morphogenetic events that includes apical cell constriction, localized alignment of groups of cells and ommatidia morphogenesis coupled to neurogenesis. Here, we use live imaging to document the sequence of adherens junction (AJ) remodelling events required to generate the fly ommatidium. In this context, we demonstrate that the kinases Rok and Drak function redundantly during Myosin II-dependent cell constriction, subsequent multicellular alignment and AJ remodelling. In addition, we show that early multicellular patterning characterized by cell alignment is promoted by the conserved transcription factor Atonal (Ato). Further ommatidium patterning requires the epidermal growth factor receptor (EGFR) signalling pathway, which transcriptionally governs rok- and Drak-dependent AJ remodelling while also promoting neurogenesis. In conclusion, our work reveals an important role for Drak in regulating AJ remodelling during retinal morphogenesis. It also sheds new light on the interplay between Ato, EGFR-dependent transcription and AJ remodelling in a system in which neurogenesis is coupled with cell shape changes and regulated steps of cell intercalation.