RESUMEN
During development, mechanical forces cause changes in size, shape, number, position, and gene expression of cells. They are therefore integral to any morphogenetic processes. Force generation by actin-myosin networks and force transmission through adhesive complexes are two self-organizing phenomena driving tissue morphogenesis. Coordination and integration of forces by long-range force transmission and mechanosensing of cells within tissues produce large-scale tissue shape changes. Extrinsic mechanical forces also control tissue patterning by modulating cell fate specification and differentiation. Thus, the interplay between tissue mechanics and biochemical signaling orchestrates tissue morphogenesis and patterning in development.
Asunto(s)
Fenómenos Biomecánicos , Morfogénesis , Actinas/metabolismo , Animales , Forma de la Célula , Miosinas/metabolismo , Transducción de SeñalRESUMEN
Understanding how development is coordinated in multiple tissues and gives rise to fully functional organs or whole organisms necessitates microscopy tools. Over the last decade numerous advances have been made in live-imaging, enabling high resolution imaging of whole organisms at cellular resolution. Yet, these advances mainly rely on mounting the specimen in agarose or aqueous solutions, precluding imaging of organisms whose oxygen uptake depends on ventilation. Here, we implemented a multi-view multi-scale microscopy strategy based on confocal spinning disk microscopy, called Multi-View confocal microScopy (MuViScopy). MuViScopy enables live-imaging of multiple organs with cellular resolution using sample rotation and confocal imaging without the need of sample embedding. We illustrate the capacity of MuViScopy by live-imaging Drosophila melanogaster pupal development throughout metamorphosis, highlighting how internal organs are formed and multiple organ development is coordinated. We foresee that MuViScopy will open the path to better understand developmental processes at the whole organism scale in living systems that require gas exchange by ventilation.
Asunto(s)
Drosophila melanogaster/anatomía & histología , Microscopía Confocal/métodos , Animales , Metamorfosis Biológica , Pupa/anatomía & histología , Imagen de Lapso de TiempoRESUMEN
During epithelial cytokinesis, the remodelling of adhesive cell-cell contacts between the dividing cell and its neighbours has profound implications for the integrity, arrangement and morphogenesis of proliferative tissues. In both vertebrates and invertebrates, this remodelling requires the activity of non-muscle myosin II (MyoII) in the interphasic cells neighbouring the dividing cell. However, the mechanisms that coordinate cytokinesis and MyoII activity in the neighbours are unknown. Here we show that in the Drosophila notum epithelium, each cell division is associated with a mechanosensing and transmission event that controls MyoII dynamics in neighbouring cells. We find that the ring pulling forces promote local junction elongation, which results in local E-cadherin dilution at the ingressing adherens junction. In turn, the reduction in E-cadherin concentration and the contractility of the neighbouring cells promote self-organized actomyosin flows, ultimately leading to accumulation of MyoII at the base of the ingressing junction. Although force transduction has been extensively studied in the context of adherens junction reinforcement to stabilize adhesive cell-cell contacts, we propose an alternative mechanosensing mechanism that coordinates actomyosin dynamics between epithelial cells and sustains the remodelling of the adherens junction in response to mechanical forces.
Asunto(s)
Actomiosina/metabolismo , Uniones Adherentes/metabolismo , Cadherinas/metabolismo , Citocinesis , Drosophila melanogaster/citología , Miosina Tipo II/metabolismo , Animales , Adhesión Celular , División Celular , Células Epiteliales/citología , Células Epiteliales/metabolismoRESUMEN
The orientation of cell division along the long axis of the interphase cell--the century-old Hertwig's rule--has profound roles in tissue proliferation, morphogenesis, architecture and mechanics. In epithelial tissues, the shape of the interphase cell is influenced by cell adhesion, mechanical stress, neighbour topology, and planar polarity pathways. At mitosis, epithelial cells usually adopt a rounded shape to ensure faithful chromosome segregation and to promote morphogenesis. The mechanisms underlying interphase cell shape sensing in tissues are therefore unknown. Here we show that in Drosophila epithelia, tricellular junctions (TCJs) localize force generators, pulling on astral microtubules and orienting cell division via the Dynein-associated protein Mud independently of the classical Pins/Gαi pathway. Moreover, as cells round up during mitosis, TCJs serve as spatial landmarks, encoding information about interphase cell shape anisotropy to orient division in the rounded mitotic cell. Finally, experimental and simulation data show that shape and mechanical strain sensing by the TCJs emerge from a general geometric property of TCJ distributions in epithelial tissues. Thus, in addition to their function as epithelial barrier structures, TCJs serve as polarity cues promoting geometry and mechanical sensing in epithelial tissues.
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Forma de la Célula , Drosophila melanogaster/citología , Células Epiteliales/citología , Uniones Intercelulares , Interfase , Mitosis , Animales , Proteínas de Ciclo Celular , Polaridad Celular , Proteínas de Drosophila/metabolismo , Células Epiteliales/metabolismo , Epitelio/metabolismo , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Inhibidores de Disociación de Guanina Nucleótido/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Microtúbulos/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
In epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored de novo formation of tricellular septate junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis.
Asunto(s)
Uniones Adherentes/metabolismo , Citocinesis , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Epitelio/metabolismo , Proteínas de la Membrana/metabolismo , Mitosis , Proteínas del Tejido Nervioso/metabolismo , Receptores Depuradores/metabolismo , Uniones Adherentes/genética , Animales , Hidrolasas de Éster Carboxílico/genética , Hidrolasas de Éster Carboxílico/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Epitelio/crecimiento & desarrollo , Proteínas de la Membrana/genética , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Proteínas del Tejido Nervioso/genética , Receptores Depuradores/genética , Tórax/crecimiento & desarrollo , Tórax/metabolismoRESUMEN
Engagement of the B cell receptor (BCR) by surface-tethered antigens (Ag) leads to formation of a synapse that promotes Ag uptake for presentation onto major histocompatibility complex class II (MHCII) molecules. We have highlighted the membrane trafficking events and associated molecular mechanisms involved in Ag extraction and processing at the B cell synapse. MHCII-containing lysosomes are recruited to the synapse where they locally undergo exocytosis, allowing synapse acidification and the extracellular release of hydrolases that promote the extraction of the immobilized Ag. Lysosome recruitment and secretion results from the polarization of the microtubule-organizing center (MTOC), which relies on the cell division cycle (Cdc42)-downstream effector, atypical protein kinase C (aPKCζ). aPKCζ is phosphorylated upon BCR engagement, associates to lysosomal vesicles, and is required for their polarized secretion at the B cell synapse. Regulation of B lymphocyte polarity therefore emerges as a central mechanism that couples Ag extraction to Ag processing and presentation.
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Presentación de Antígeno , Linfocitos B/inmunología , Sinapsis Inmunológicas , Lisosomas , Receptores de Antígenos de Linfocitos B/fisiología , Animales , Polaridad Celular , Lisosomas/metabolismo , Ratones , Proteína Quinasa C/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Proteína de Unión al GTP cdc42/inmunologíaRESUMEN
Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known about the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in Drosophila) is best known for its role in spindle orientation. Here, we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in Drosophila epithelial cells. We found that Dynein and Mud mainly initiate centrosome-spindle coupling prior to nuclear envelope breakdown (NEB) by promoting correct centrosome positioning or separation, while Asp acts largely independently of Dynein and Mud to maintain centrosome-spindle coupling. Failure in the centrosome-spindle coupling leads to mis-segregation of the two centrosomes into one daughter cell, resulting in cells with supernumerary centrosomes during subsequent divisions. Altogether, we propose that Dynein, Mud and Asp operate sequentially during the cell cycle to ensure efficient centrosome-spindle coupling in mitosis, thereby preventing centrosome mis-segregation to maintain centrosome number.
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Proteínas de Drosophila/fisiología , Drosophila melanogaster/metabolismo , Dineínas/fisiología , Proteínas de la Membrana/fisiología , Proteínas Asociadas a Microtúbulos/fisiología , Proteínas del Tejido Nervioso/fisiología , Animales , Centrosoma/metabolismo , Segregación Cromosómica , Drosophila melanogaster/citología , Células Epiteliales/metabolismo , Mitosis , Transporte de Proteínas , Pupa/citología , Pupa/metabolismoRESUMEN
Tumor suppressors and proto-oncogenes play crucial roles in tissue proliferation. Furthermore, de-regulation of their functions is deleterious to tissue architecture and can result in the sorting of somatic rounded clones minimizing their contact with surrounding wild-type (wt) cells. Defects in the shape of somatic clones correlate with defects in proliferation, cell affinity, cell-cell adhesion, oriented cell division and cortical contractility. Combining genetics, live-imaging, laser ablation and computer simulations, we aim to analyze whether distinct or similar mechanisms can account for the common role of tumor suppressors and proto-oncogenes in cell-cell contact regulation. In Drosophila epithelia, the tumor suppressors Fat (Ft) and Dachsous (Ds) regulate cell proliferation, tissue morphogenesis, planar cell polarity and junction tension. By analyzing the evolution over time of ft mutant cells and clones, we show that ft clones reduce their cell-cell contacts with the surrounding wt tissue in the absence of concomitant cell divisions and over-proliferation. This contact reduction depends on opposed changes of junction tensions in the clone bulk and its boundary with neighboring wt tissue. More generally, either clone bulk or boundary junction tension is modulated by the activation of Yorkie, Myc and Ras, yielding similar contact reductions with wt cells. Together, our data highlight mechanical roles for proto-oncogene and tumor suppressor pathways in cell-cell interactions.
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Comunicación Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proto-Oncogenes , Proteínas Supresoras de Tumor/metabolismo , Animales , Moléculas de Adhesión Celular/metabolismo , División Celular , Polaridad Celular , Proliferación Celular , Forma de la Célula , Células Clonales , Drosophila melanogaster/citología , Uniones Intercelulares/metabolismo , Mutación , Miosinas/metabolismo , Imagen de Lapso de TiempoRESUMEN
γ-Tubulin is critical for microtubule (MT) assembly and organization. In metazoa, this protein acts in multiprotein complexes called γ-Tubulin Ring Complexes (γ-TuRCs). While the subunits that constitute γ-Tubulin Small Complexes (γ-TuSCs), the core of the MT nucleation machinery, are essential, mutation of γ-TuRC-specific proteins in Drosophila causes sterility and morphological abnormalities via hitherto unidentified mechanisms. Here, we demonstrate a role of γ-TuRCs in controlling spindle orientation independent of MT nucleation activity, both in cultured cells and in vivo, and examine a potential function for γ-TuRCs on astral MTs. γ-TuRCs locate along the length of astral MTs, and depletion of γ-TuRC-specific proteins increases MT dynamics and causes the plus-end tracking protein EB1 to redistribute along MTs. Moreover, suppression of MT dynamics through drug treatment or EB1 down-regulation rescues spindle orientation defects induced by γ-TuRC depletion. Therefore, we propose a role for γ-TuRCs in regulating spindle positioning by controlling the stability of astral MTs.
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Proteínas Asociadas a Microtúbulos/fisiología , Microtúbulos/metabolismo , Huso Acromático/fisiología , Tubulina (Proteína)/fisiología , Animales , Animales Modificados Genéticamente , Células Cultivadas , Drosophila , Células HeLa , Humanos , Complejos Multiproteicos/fisiologíaRESUMEN
Organ shaping and patterning depends on the coordinated regulation of multiple processes. The Drosophila compound eye provides an excellent model to study the coordination of cell fate and cell positioning during morphogenesis. Here, we find that loss of vav oncogene function during eye development is associated with a disorganised retina characterised by the presence of additional cells of all types. We demonstrate that these defects result from two distinct roles of Vav. First, and in contrast to its well-established role as a positive effector of the EGF receptor (EGFR), we show that readouts of the EGFR pathway are upregulated in vav mutant larval eye disc and pupal retina, indicating that Vav antagonises EGFR signalling during eye development. Accordingly, decreasing EGFR signalling in vav mutant eyes restores retinal organisation and rescues most vav mutant phenotypes. Second, using live imaging in the pupal retina, we observe that vav mutant cells do not form stable adherens junctions, causing various defects, such as recruitment of extra primary pigment cells. In agreement with this role in junction dynamics, we observe that these phenotypes can be exacerbated by lowering DE-Cadherin or Cindr levels. Taken together, our findings establish that Vav acts at multiple times during eye development to prevent excessive cell recruitment by limiting EGFR signalling and by regulating junction dynamics to ensure the correct patterning and morphogenesis of the Drosophila eye.
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Uniones Adherentes/metabolismo , Receptores ErbB/metabolismo , Ojo/metabolismo , Proteínas Proto-Oncogénicas c-vav/metabolismo , Animales , Tipificación del Cuerpo/genética , Tipificación del Cuerpo/fisiología , Cadherinas/genética , Cadherinas/metabolismo , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Receptores ErbB/genética , Ojo/embriología , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Morfogénesis/genética , Morfogénesis/fisiología , Proteínas Proto-Oncogénicas c-vav/genética , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Asymmetric cell division generates cell fate diversity during development and adult life. Recent findings have demonstrated that during stem cell divisions, the movement of centrosomes is asymmetric in prophase and that such asymmetry participates in mitotic spindle orientation and cell polarization. Here, we have investigated the dynamics of centrosomes during Drosophila sensory organ precursor asymmetric divisions and find that centrosome movements are asymmetric during cytokinesis. We demonstrate that centrosome movements are controlled by the cell fate determinant Numb, which does not act via its classical effectors, Sanpodo and α-Adaptin, but via the Collapsin Response Mediator Protein (CRMP). Furthermore, we find that CRMP is necessary for efficient Notch signalling and that it regulates the duration of the pericentriolar accumulation of Rab11-positive endosomes, through which the Notch ligand, Delta is recycled. Our work characterizes an additional mode of asymmetric centrosome movement during asymmetric divisions and suggests a model whereby the asymmetry in centrosome movements participates in differential Notch activation to regulate cell fate specification.
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Centrosoma/metabolismo , Proteínas de Drosophila/metabolismo , Hormonas Juveniles/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Órganos de los Sentidos/citología , Células Madre/citología , Células Madre/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Drosophila , Proteínas de Drosophila/genética , Inmunoprecipitación , Hormonas Juveniles/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
The mechanisms underlying endosomal trafficking have been mostly dissected in yeast and mammalian tissue culture cells. Here, we review recent advances in the understanding of the role of endosomal trafficking in Drosophila epithelial cells. We focus on endosomal pathways that control cell polarization, cell growth, cell fate and epithelial cell rearrangement. We expect that mechanistic studies in mammalian cells and functional studies in invertebrates will continue to synergize to provide a comprehensive view of the role of endosomal trafficking in epithelial tissue organization and functions.
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Endosomas/fisiología , Células Epiteliales/fisiología , Animales , División Celular/fisiología , Aumento de la Célula , Drosophila , Transporte de Proteínas/fisiologíaRESUMEN
Applying mechanical forces to tissues helps to understand morphogenesis and homeostasis. Additionally, recording the dynamics of living tissues under mechanical constraints is needed to explore tissue biomechanics. Here, we present a protocol to 3D-print a StretchCo device and use it to apply uniaxial mechanical stress on the Drosophila pupal dorsal thorax epithelium. We describe steps for 3D printing, polydimethylsiloxane (PDMS) strip cutting, and glue preparation. We detail procedures for PDMS strip mounting, tissue compaction, and live imaging upon force application. For additional details on the use and execution of this protocol, please refer to Cachoux et al. (2023)1 from which the StretchCo machine has been derived.
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Dimetilpolisiloxanos , Drosophila , Animales , Epitelio , Morfogénesis , Fenómenos Biomecánicos , Estrés MecánicoRESUMEN
The cell cortex of syncytial Drosophila embryos is patterned into cap and intercap regions by centrosomes, specific sets of proteins that are restricted to their respective regions by unknown mechanisms. Here, we found that Kinesin-1 is required for the restriction of plus- and minus-ends of centrosomal and non-centrosomal microtubules to the cap region, marked by EB1 and Patronin/Shot, respectively. Kinesin-1 also directly or indirectly restricts proteins and Rho signaling to the intercap, including the RhoGEF Pebble, Dia, Myosin II, Capping protein-α, and the polarity protein Par-1. Furthermore, we found that Par-1 is required for cap restriction of Patronin/Shot, and vice versa Patronin, for Par-1 enrichment at the intercap. In summary, our data support a model that Kinesin-1 would mediate the restriction of centrosomal and non-centrosomal microtubules to a region close to the centrosomes and exclude Rho signaling and Par-1. In addition, mutual antagonistic interactions would refine and maintain the boundary between cap and intercap and thus generate a distinct cortical pattern.
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Proteínas de Drosophila , Drosophila , Glucógeno Sintasa Quinasa 3 , Cinesinas , Proteínas de la Membrana , Animales , Centrosoma , Proteínas del Citoesqueleto , Drosophila/embriología , Drosophila/genética , Proteínas de Drosophila/genética , Glucógeno Sintasa Quinasa 3/genética , Cinesinas/genética , Proteínas Asociadas a Microtúbulos/genética , Transducción de Señal , Proteínas de la Membrana/genéticaRESUMEN
Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.
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Proteínas de Drosophila , Animales , Proteínas de Drosophila/genética , Drosophila/genética , Epitelio , Morfogénesis/genéticaRESUMEN
Cell proliferation is central to epithelial tissue development, repair, and homeostasis. During cell division, small RhoGTPases control both actomyosin dynamics and cell-cell junction remodeling to faithfully segregate the genome while maintaining tissue polarity and integrity. To decipher the mechanisms of RhoGTPase spatiotemporal regulation during epithelial cell division, we generated a transgenic fluorescently tagged library for the 48 Drosophila Rho guanine exchange factors (RhoGEFs) and GTPase-activating proteins (GAPs), and we systematically characterized their endogenous distributions by time-lapse microscopy. Therefore, we unveiled candidate regulators of the interplay between actomyosin and junctional dynamics during epithelial cell division. Building on these findings, we established that the conserved RhoGEF Cysts and RhoGEF4 play sequential and distinct roles to couple cytokinesis with de novo junction formation. During ring contraction, Cysts via Rho1 participates in the neighbor mechanosensing response, promoting daughter-daughter cell membrane juxtaposition in preparation to de novo junction formation. Subsequently and upon midbody formation, RhoGEF4 via Rac acts in the dividing cell to ensure the withdrawal of the neighboring cell membranes, thus controlling de novo junction length and cell-cell arrangements upon cytokinesis. Altogether, our findings delineate how the RhoGTPases Rho and Rac are locally and temporally activated during epithelial cytokinesis, highlighting the RhoGEF/GAP library as a key resource to understand the broad range of biological processes regulated by RhoGTPases.
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Actomiosina , Células Epiteliales , Animales , Factores de Intercambio de Guanina Nucleótido Rho/genética , Factores de Intercambio de Guanina Nucleótido Rho/metabolismo , Actomiosina/metabolismo , División Celular , Citocinesis , DrosophilaRESUMEN
Geometry is a fundamental attribute of biological systems, and it underlies cell and tissue dynamics. Cell geometry controls cell-cycle progression and mitosis and thus modulates tissue development and homeostasis. In sharp contrast and despite the extensive characterization of the genetic mechanisms of caspase activation, we know little about whether and how cell geometry controls apoptosis commitment in developing tissues. Here, we combined multiscale time-lapse microscopy of developing Drosophila epithelium, quantitative characterization of cell behaviors, and genetic and mechanical perturbations to determine how apoptosis is controlled during epithelial tissue development. We found that early in cell lives and well before extrusion, apoptosis commitment is linked to two distinct geometric features: a small apical area compared with other cells within the tissue and a small relative apical area with respect to the immediate neighboring cells. We showed that these global and local geometric characteristics are sufficient to recapitulate the tissue-scale apoptotic pattern. Furthermore, we established that the coupling between these two geometric features and apoptotic cells is dependent on the Hippo/YAP and Notch pathways. Overall, by exploring the links between cell geometry and apoptosis commitment, our work provides important insights into the spatial regulation of cell death in tissues and improves our understanding of the mechanisms that control cell number and tissue size.
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Apoptosis , Drosophila , Animales , Epitelio/fisiología , Drosophila/genética , Apoptosis/fisiología , Muerte Celular , Mitosis , Células EpitelialesRESUMEN
The maintenance of neural stem cells (NSCs) in the adult brain depends on their activation frequency and division mode. Using long-term intravital imaging of NSCs in the zebrafish adult telencephalon, we reveal that apical surface area and expression of the Notch ligand DeltaA predict these NSC decisions. deltaA-negative NSCs constitute a bona fide self-renewing NSC pool and systematically engage in asymmetric divisions generating a self-renewing deltaAneg daughter, which regains the size and behavior of its mother, and a neurogenic deltaApos daughter, eventually engaged in neuronal production following further quiescence-division phases. Pharmacological and genetic manipulations of Notch, DeltaA, and apical size further show that the prediction of activation frequency by apical size and the asymmetric divisions of deltaAneg NSCs are functionally independent of Notch. These results provide dynamic qualitative and quantitative readouts of NSC lineage progression in vivo and support a hierarchical organization of NSCs in differently fated subpopulations.
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Células-Madre Neurales , Pez Cebra , Animales , Neuronas/fisiología , División Celular , NeurogénesisRESUMEN
The generation of daughter cells of different fate and size depends on the orientation, positioning and morphology of the mitotic spindle. In both C. elegans and Drosophila, heterotrimeric G proteins have emerged as central and conserved regulators of this process. Although the same molecular players are involved in worms and flies, there are clear differences in the mechanisms used. Interestingly, recent work in mammalian cells suggests that heterotrimeric G proteins may control spindle positioning in higher organisms during symmetric and asymmetric cell divisions.