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International audience; Apoptosis plays an important role in morphogenesis, and the notion that apoptotic cells can impact their surroundings came to light recently. However, how this applies to vertebrate morphogenesis remains unknown. Here, we use the formation of the neural tube to determine how apoptosis contributes to morphogenesis in vertebrates. Neural tube closure defects have been reported when apoptosis is impaired in vertebrates, although the cellular mechanisms involved are unknown. Using avian embryos, we found that apoptotic cells generate an apico-basal force before being extruded from the neuro-epithelium. This force, which relies on a contractile actomyosin cable that extends along the apico-basal axis of the cell, drives nuclear fragmentation and influences the neighboring tissue. Together with the morphological defects observed when apoptosis is prevented, these data strongly suggest that the neuroepithelium keeps track of the mechanical impact of apoptotic cells and that the apoptotic forces, cumulatively, contribute actively to neural tube bending.

International audience; Apoptosis, or programmed cell death, is a form of cell suicide that is extremely important for ridding the body of cells that are no longer required, to protect the body against hazardous cells, such as cancerous ones, and to promote tissue morphogenesis during animal development. Upon reception of a death stimulus, the doomed cell activates biochemical pathways that eventually converge on the activation of dedicated enzymes, caspases. Numerous pieces of information on the biochemical control of the process have been gathered, from the successive events of caspase activation to the identification of their targets, such as lamins, which constitute the nuclear skeleton. Yet, evidence from multiple systems now shows that apoptosis is also a mechanical process, which may even ultimately impinge on the morphogenesis of the surrounding tissues. This mechanical role relies on dramatic actomyosin cytoskeleton remodelling, and on its coupling with the nucleus before nucleus fragmentation. Here, we provide an overview of apoptosis before describing how apoptotic forces could combine with selective caspase-dependent proteolysis to orchestrate nucleus destruction.

It is now well established that apoptosis is induced in response to mechanical strain. Indeed, increasing compressive forces induces apoptosis in confined spheroids of tumour cells, whereas releasing stress reduces apoptosis in spheroids cultivated in free suspension (Cheng et al., 2009). Apoptosis can also be induced by applying a 100 to 250MPa pressure, as shown in different cultured cells (for review, see (Frey et al., 2008)). During epithelium development, the pressure caused by a fast-growing clone can trigger apoptosis at the vicinity of the clone, mediating mechanical cell competition (Levayer et al., 2016). While the effect of strain has long been known for its role in apoptosis induction, the reciprocal mechanism has only recently been highlighted. First demonstrated at the cellular level, the effect of an apoptotic cell on its direct neighbours has been analysed in different kinds of monolayer epithelium (Gu et al., 2011; Rosenblatt et al., 2001; Kuipers et al., 2014; Lubkov & Bar-Sagi, 2014). More recently, the concept of a broader impact of apoptotic cell behaviours on tissue mechanical strain has emerged from the characterisation of tissue remodelling during Drosophila development (Toyama et al., 2008; Monier et al., 2015). In the present review, we summarize our current knowledge on the mechanical impact of apoptosis during tissue remodelling.

© 2015 Macmillan Publishers Limited. All rights reserved. Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension., Agence Nationale de la Recherche (ANR), Fondation de la Recherche et de l’Innovation The´rapeutique en Cance´rologie (RITC) and the University of Toulouse.

Far from being passive, apoptotic cells influence their environment. For example, they promote tissue folding, myoblast fusion and modulate tumor growth. Understanding the role of apoptotic cells necessitates their efficient tracking within living tissues, a task that is currently challenging. In order to easily spot apoptotic cells in developing

Far from being passive, apoptotic cells influence their environment. For instance, they promote tissue folding, myoblast fusion and modulate tumor growth. Understanding the role of apoptotic cells necessitates their efficient tracking within living tissues, a task which is currently challenging. In order to easily spot apoptotic cells in developing Drosophila tissues, we generated a series of fly lines expressing different fluorescent sensors of caspase activity. We show that three of these reporters (GFP, Cerulean and Venus derived molecules) are detected specifically in apoptotic cells and throughout the whole process of programmed cell death. These reporters allow the specific visualization of apoptotic cells directly within living tissues, without any post-acquisition processing. They overcome the limitations of other apoptosis detection methods developed so far and notably, they can be combined with any kind of fluorophore.

In summary, the patterning of the presumptive leg depends on gradients of Dpp and Wg morphogens, which lead to the establishment of the proximo-distal axis marked by the expression of Hth, Dac and Dll in broad domains along the leg. Then, EGFR signaling specifies the tarsal region by regulating the expression of tarsal gap genes in different tarsal segments. This patterning is closely linked to the formation of rings of Notch activation in the distal part of each leg segment. These rings of Notch activation are further regulated by different mechanisms: (1) the maintenance of a sharp border of Dl expression, (2) the inhibition of N activation in cells located proximally to the ligands, thus restricting N activity specifically to the distal part of cells. This localised activation of Notch induces the expression of Dysfusion which controls the expression of both pro-apoptotic genes and RhoGTPase regulators. Finally, apoptotic cells appear within the pro-apoptotic domain, and while dying, generate a transient pulling force. This force constitutes a mechanical signal that propagates to the rest of the tissue and triggers cytoskeleton reorganisation specifically in the presumptive fold, where RhoGTPase regulators are expressed. Altogether, this complex array of patterning and signaling leads to precise cellular mapping of the developing leg to correctly position local cell shape modifications, inducing tissue folding.

Beyond safeguarding the organism from cell misbehavior and controlling cell number, apoptosis (or programmed cell death) plays key roles during animal development. In particular, it has long been acknowledged that apoptosis participates in tissue remodeling. Yet, until recently, this contribution to morphogenesis was considered as "passive," consisting simply in the local removal of unnecessary cells leading to a new shape. In recent years, applying live imaging methods to study the dynamics of apoptosis in various contexts has considerably modified our vision, revealing that in fact, dying cells remodel their neighborhood actively. Here, we first focus on the intrinsic cellular properties of apoptotic cells during their dismantling, in particular the role of the cytoskeleton during their characteristic morphological changes. Second, we review the various roles of apoptosis during developmental morphogenetic processes and pinpoint the crucial role of live imaging in revealing new concepts, in particular apoptosis as a generator of mechanical forces to control tissue dynamics.

Morphogens are secreted signalling molecules that govern many developmental processes. In the Drosophila wing disc, the transforming growth factor beta (TGFbeta) homologue Decapentaplegic (Dpp) forms a smooth gradient and specifies cell fate by conferring a defined value of morphogen activity. Thus, neighbouring cells have similar amounts of Dpp protein, and if a sharp discontinuity in Dpp activity is generated between these cells, Jun kinase (JNK)-dependent apoptosis is triggered to restore graded positional information. To date, it has been assumed that this apoptotic process is only activated when normal signalling is distorted. However, we now show that a similar process occurs during normal development: rupture in Dpp activity occurs during normal segmentation of the distal legs of Drosophila. This sharp boundary of Dpp signalling, independently of the absolute level of Dpp activity, induces a JNK-reaper-dependent apoptosis required for the morphogenesis of a particular structure of the leg, the joint. Our results show that Dpp could induce a developmental programme not only in a concentration dependent manner, but also by the creation of a sharp boundary of Dpp activity. Furthermore, the same process could be used either to restore a normal pattern in response to artificial disturbance or to direct a morphogenetic process.

The development of the Drosophila leg is a good model to study processes of pattern formation, cell death and segmentation. Such processes require the coordinate activity of different genes and signaling pathways that progressively subdivide the leg territory into smaller domains. One of the main pathways needed for leg development is the Notch pathway, required for determining the proximo-distal axis of the leg and for the formation of the joints that separate different leg segments. The mechanisms required to coordinate such events are largely unknown. We describe here that the zinc finger homeodomain-2 (zfh-2) gene is highly expressed in cells that will form the leg joints and needed to establish a correct size and pattern in the distal leg. There is an early requirement of zfh-2 to establish the correct proximo-distal axis, but zfh-2 is also needed at late third instar to form the joint between the fourth and fifth tarsal segments. The expression of zfh-2 requires Notch activity but zfh-2 is necessary, in turn, to activate Notch targets such as Enhancer of split and big brain. zfh-2 is controlled by the Drosophila activator protein 2 gene and regulates the late expression of tarsal-less. In the absence of zfh-2 many cells ectopically express the pro-apoptotic gene head involution defective, activate caspase-3 and are positive for acridine orange, indicating they undergo apoptosis. Our results demonstrate the key role of zfh-2 in the control of cell death and Notch signaling during leg development., The work was supported by grants from the Ministerio de Ciencia e Innovación (BMC2005-04342, BFU2008-00632 and BFU2011-26075), the Consolider Program (CSD2007-0008) and an Institutional Grant from the Ramon Areces Foundation to E.S, the Agence Nationale de la Recherche Programme (2010-JCJC-1208-01) to M.S. and NIH to K.E. H.S. is an Investigator of the Howard Hughes Medical Institute. A.G. and C.M. were supported by Spanish FPU fellowships and A.G. by a Company of Biologist Traveling Fellowship.

International audience; Handed asymmetry in organ shape and positioning is a common feature among bilateria, yet little is known about the morphogenetic mechanisms underlying left-right (LR) organogenesis. We utilize the directional 360° clockwise rotation of genitalia in Drosophila to study LR-dependent organ looping. Using time-lapse imaging, we show that rotation of genitalia by 360° results from an additive process involving two ring-shaped domains, each undergoing 180° rotation. Our results show that the direction of rotation for each ring is autonomous and strictly depends on the LR determinant myosin ID (MyoID). Specific inactivation of MyoID in one domain causes rings to rotate in opposite directions and thereby cancels out the overall movement. We further reveal a specific pattern of apoptosis at the ring boundaries and show that local cell death is required for the movement of each domain, acting as a brake-releaser. These data indicate that organ looping can proceed through an incremental mechanism coupling LR determination and apoptosis. Furthermore, they suggest a model for the stepwise evolution of genitalia posture in Diptera, through the emergence and duplication of a 180° LR module.

Summary Mechanical forces are critical regulators of cell shape changes and developmental morphogenetic processes. Forces generated along the epithelium apico-basal cell axis have recently emerged as essential for tissue remodeling in three dimensions. Yet the cellular machinery underlying those orthogonal forces remains poorly described. We found that during Drosophila leg folding cells eventually committed to die produce apico-basal forces through the formation of a dynamic actomyosin contractile tether connecting the apical surface to a basally relocalized nucleus. We show that the nucleus is anchored to basal adhesions by a basal F-actin network and constitutes an essential component of the force-producing machinery. Finally, we demonstrate force transmission to the apical surface and the basal nucleus by laser ablation. Thus, this work reveals that the nucleus, in addition to its role in genome protection, actively participates in mechanical force production and connects the contractile actomyosin cytoskeleton to basal adhesions.

Summary What regulates the spatiotemporal distribution of cell elimination in tissues remains largely unknown. This is particularly relevant for epithelia with high rates of cell elimination where simultaneous death of neighboring cells could impair epithelial sealing. Here, using the Drosophila pupal notum (a single-layer epithelium) and a new optogenetic tool to trigger caspase activation and cell extrusion, we first showed that death of clusters of at least three cells impaired epithelial sealing; yet, such clusters were almost never observed in vivo. Accordingly, statistical analysis and simulations of cell death distribution highlighted a transient and local protective phase occurring near every cell death. This protection is driven by a transient activation of ERK in cells neighboring extruding cells, which inhibits caspase activation and prevents elimination of cells in clusters. This suggests that the robustness of epithelia with high rates of cell elimination is an emerging property of local ERK feedback., Graphical abstract, Highlights • Simultaneous elimination of three neighboring cells is detrimental for epithelia • Biased cell-death distribution prevents the appearance of such clusters • This bias is driven by ERK pulses and caspase inhibition in the neighbors of dying cells • Clusters of elimination and transient sealing defects appear upon EGFR/ERK inhibition, How epithelia fine-tune the spatiotemporal distribution of cell death and cope with high rates of elimination remains unclear. Valon et al. shows that pulses of ERK induced near every dying cell prevent the simultaneous elimination of neighboring cells, hence maintaining epithelial sealing despite the high rates of cell elimination.

Each animal species acquires a specific shape during development. The generation of mechanical forces is one of the strategies used by cells to sculpt organs. During animal development, the mechanical forces generated in the plane of adherens junctions are important for epithelium remodeling. These planar forces have been extensively studied over the last years. This is particularly the case during apical constriction of mesodermal cells during drosophila embryo gastrulation. The reduction of the cell's apex is considered a fundamental process to trigger invagination of this tissue. However, recently, it has been shown that forces can also be generated along the cell apico-basal axis. The team in which I did my thesis has shown that these forces are important for the formation of folds during drosophila leg development. In this process, before their disappearance, cells form an apico-basal myosin structure, called "myosin cable". The force created by the contraction of the cable is transmitted to the cell's neighbors, inducing cell shape changes progressively resulting in fold formation. However, the mechanisms required for apico-basal force generation remained unknown. The goal of my thesis was to study in detail how the cells destined to die could generate an effective force. We made the hypothesis that the myosin cable should be anchored at the apical and basal cell poles in order to promote a resistance to the cable contraction, and to allow force transmission to the neighbors. Therefore, my aim was to identify these anchoring points thanks to imaging and genetics technics. First, I had identified apical anchor point. Indeed, apoptotic cells reduce their apex but maintain their adherens junctions. The apical extremity of the myosin cable colocalizes to this adhesion structure. Secondly, I searched for the basal anchor point of myosin cable. Surprisingly, I observed that the nucleus of apoptotic cells is systematically relocated on the basal cell half and that the myosin cable contacts it. I tested whether the nucleus plays a role in myosin cable anchorage by perturbing its basal localization. The loss of function of Klarsicht, a LINC complex protein, prevents the cell to deform its neighbors, showing that, in this context the force is strongly or totally abolished. Finally, I have shown that the apoptotic nucleus itself is anchored to the basal side in order to promote a resistance during cable contraction. Indeed, I studied nuclei mobility and showed that apoptotic nuclei are less mobile than non-apoptotic nuclei. I also showed that F-actin and Talin, a basal adhesion component, are required for apoptotic nucleus stability. Furthermore, I have observed that, during cable contraction, the nucleus moves back apically and that it deforms locally. Finally, laser ablation experiments of the myosin cable show an apical recoil of apical surface and a basal recoil of the nucleus. Thus, the force generated by the apoptotic cells is transmitted in the apico-basal axis thanks to the link between apical adherence, cable and nucleus. My work highlights a new mechanism of force generation. This new mechanism of apico-basal force could be conserved in other cell types in additional invagination processes during morphogenesis. My results also show that the nucleus plays a new role, beyond the protection of the genome, by participating actively in force generation., Chaque espèce vivante acquiert une forme qui lui est propre. La génération de forces mécaniques est l'une des stratégies utilisées par les cellules pour sculpter les organes. Lors du développement animal, les forces mécaniques générées dans le plan des jonctions adhérentes sont importantes pour le remodelage des tissus épithéliaux. Ces forces planaires ont été particulièrement étudiées ces dernières années. C'est le cas notamment de la constriction apicale des cellules lors de l'invagination du mésoderme de l'embryon de drosophile. La réduction de l'apex des cellules est considérée comme un processus fondamental pour la formation de la pliure initiale de cet épithélium. Toutefois, il a été découvert récemment que des forces peuvent aussi être générées dans l'axe apico-basal des cellules. L'équipe dans laquelle j'ai effectué ma thèse a montré que de telles forces sont requises pour la formation de plis dans la patte de la drosophile lors de son développement. Dans ce processus, avant de disparaitre par apoptose (ou mort programmée), les cellules vont former une structure apico-basale appelé "câble de myosine" qui, en se contractant, va induire une déformation des cellules voisines, aboutissant progressivement à la formation de plis. Cependant, les mécanismes requis pour la génération de la force apico-basale restaient inconnus. L'objectif de ma thèse était donc de chercher comment ces cellules destinées à mourir pouvaient générer une force efficace. L'hypothèse de travail était que ce câble de myosine devait être ancré au pôle apical et au pôle basal de la cellule afin de fournir une résistance permettant la génération d'une force efficace pouvant être transmise aux cellules voisines. J'ai donc cherché à identifier ces points d'ancrage grâce à des techniques d'imagerie et de génétique. Dans un premier temps, j'ai identifié le point d'ancrage apical du câble. En effet, les cellules apoptotiques réduisent leur apex mais conservent leurs jonctions adhérentes au niveau desquelles co-localise l'extrémité apicale du câble de myosine. Dans un deuxième temps, j'ai cherché quel pourrait être le point d'ancrage basal du câble de myosine. Une observation surprenante montre que le noyau des cellules apoptotiques est systématiquement relocalisé au pôle basal et que le câble de myosine rentre en contact avec lui. J'ai testé si le noyau joue un rôle dans l'ancrage du câble de myosine en perturbant sa localisation basale. La perte de fonction de Klarsicht, une protéine du complexe LINC, empêche la cellule d'induire une déformation des cellules voisines, montrant que dans ce contexte où le noyau n'est pas relocalisé au pôle basal de la cellule, la force n'est pas ou peu produite. Finalement, j'ai pu montrer que le noyau est lui-même ancré au pôle basal de la cellule afin de fournir un point de résistance lors de la contraction du câble. En effet, j'ai étudié la mobilité des noyaux, montrant d'une part que les noyaux apoptotiques sont moins mobiles que ceux des cellules non-apoptotiques et, d'autre part, que l'actine et la Taline, un composant des adhésions basales, sont requises pour la stabilisation du noyau apoptotique. De plus, j'ai observé que, lors de la contraction du câble, le noyau remonte simultanément et que celui-ci se déforme localement. Finalement, des expériences d'ablation laser du câble de myosine montrent un relâchement de la surface apicale et un recul du noyau. Ainsi, la force émise par les cellules apoptotiques est transmise dans l'axe apico-basal par une liaison adhérence apicale-câble-noyau. Mon travail met en lumière un mécanisme original de génération de force. Ce nouveau mécanisme de force apico-basale pourrait être conservé dans d'autres types cellulaires engagés dans des processus d'invagination au cours de la morphogenèse. Mes résultats montrent également que le noyau joue un rôle nouveau, au-delà de son rôle de protection du génome, en participant activement à la génération d'une force.

Each animal species acquires a specific shape during development. The generation of mechanical forces is one of the strategies used by cells to sculpt organs. During animal development, the mechanical forces generated in the plane of adherens junctions are important for epithelium remodeling. These planar forces have been extensively studied over the last years. This is particularly the case during apical constriction of mesodermal cells during drosophila embryo gastrulation. The reduction of the cell's apex is considered a fundamental process to trigger invagination of this tissue. However, recently, it has been shown that forces can also be generated along the cell apico-basal axis. The team in which I did my thesis has shown that these forces are important for the formation of folds during drosophila leg development. In this process, before their disappearance, cells form an apico-basal myosin structure, called "myosin cable". The force created by the contraction of the cable is transmitted to the cell's neighbors, inducing cell shape changes progressively resulting in fold formation. However, the mechanisms required for apico-basal force generation remained unknown. The goal of my thesis was to study in detail how the cells destined to die could generate an effective force. We made the hypothesis that the myosin cable should be anchored at the apical and basal cell poles in order to promote a resistance to the cable contraction, and to allow force transmission to the neighbors. Therefore, my aim was to identify these anchoring points thanks to imaging and genetics technics. First, I had identified apical anchor point. Indeed, apoptotic cells reduce their apex but maintain their adherens junctions. The apical extremity of the myosin cable colocalizes to this adhesion structure. Secondly, I searched for the basal anchor point of myosin cable. Surprisingly, I observed that the nucleus of apoptotic cells is systematically relocated on the basal cell half and that the myosin cable contacts it. I tested whether the nucleus plays a role in myosin cable anchorage by perturbing its basal localization. The loss of function of Klarsicht, a LINC complex protein, prevents the cell to deform its neighbors, showing that, in this context the force is strongly or totally abolished. Finally, I have shown that the apoptotic nucleus itself is anchored to the basal side in order to promote a resistance during cable contraction. Indeed, I studied nuclei mobility and showed that apoptotic nuclei are less mobile than non-apoptotic nuclei. I also showed that F-actin and Talin, a basal adhesion component, are required for apoptotic nucleus stability. Furthermore, I have observed that, during cable contraction, the nucleus moves back apically and that it deforms locally. Finally, laser ablation experiments of the myosin cable show an apical recoil of apical surface and a basal recoil of the nucleus. Thus, the force generated by the apoptotic cells is transmitted in the apico-basal axis thanks to the link between apical adherence, cable and nucleus. My work highlights a new mechanism of force generation. This new mechanism of apico-basal force could be conserved in other cell types in additional invagination processes during morphogenesis. My results also show that the nucleus plays a new role, beyond the protection of the genome, by participating actively in force generation.; Chaque espèce vivante acquiert une forme qui lui est propre. La génération de forces mécaniques est l'une des stratégies utilisées par les cellules pour sculpter les organes. Lors du développement animal, les forces mécaniques générées dans le plan des jonctions adhérentes sont importantes pour le remodelage des tissus épithéliaux. Ces forces planaires ont été particulièrement étudiées ces dernières années. C'est le cas notamment de la constriction apicale des cellules lors de l'invagination du mésoderme de l'embryon de drosophile. La réduction de l'apex des cellules est considérée comme un processus fondamental pour la formation de la pliure initiale de cet épithélium. Toutefois, il a été découvert récemment que des forces peuvent aussi être générées dans l'axe apico-basal des cellules. L'équipe dans laquelle j'ai effectué ma thèse a montré que de telles forces sont requises pour la formation de plis dans la patte de la drosophile lors de son développement. Dans ce processus, avant de disparaitre par apoptose (ou mort programmée), les cellules vont former une structure apico-basale appelé "câble de myosine" qui, en se contractant, va induire une déformation des cellules voisines, aboutissant progressivement à la formation de plis. Cependant, les mécanismes requis pour la génération de la force apico-basale restaient inconnus. L'objectif de ma thèse était donc de chercher comment ces cellules destinées à mourir pouvaient générer une force efficace. L'hypothèse de travail était que ce câble de myosine devait être ancré au pôle apical et au pôle basal de la cellule afin de fournir une résistance permettant la génération d'une force efficace pouvant être transmise aux cellules voisines. J'ai donc cherché à identifier ces points d'ancrage grâce à des techniques d'imagerie et de génétique. Dans un premier temps, j'ai identifié le point d'ancrage apical du câble. En effet, les cellules apoptotiques réduisent leur apex mais conservent leurs jonctions adhérentes au niveau desquelles co-localise l'extrémité apicale du câble de myosine. Dans un deuxième temps, j'ai cherché quel pourrait être le point d'ancrage basal du câble de myosine. Une observation surprenante montre que le noyau des cellules apoptotiques est systématiquement relocalisé au pôle basal et que le câble de myosine rentre en contact avec lui. J'ai testé si le noyau joue un rôle dans l'ancrage du câble de myosine en perturbant sa localisation basale. La perte de fonction de Klarsicht, une protéine du complexe LINC, empêche la cellule d'induire une déformation des cellules voisines, montrant que dans ce contexte où le noyau n'est pas relocalisé au pôle basal de la cellule, la force n'est pas ou peu produite. Finalement, j'ai pu montrer que le noyau est lui-même ancré au pôle basal de la cellule afin de fournir un point de résistance lors de la contraction du câble. En effet, j'ai étudié la mobilité des noyaux, montrant d'une part que les noyaux apoptotiques sont moins mobiles que ceux des cellules non-apoptotiques et, d'autre part, que l'actine et la Taline, un composant des adhésions basales, sont requises pour la stabilisation du noyau apoptotique. De plus, j'ai observé que, lors de la contraction du câble, le noyau remonte simultanément et que celui-ci se déforme localement. Finalement, des expériences d'ablation laser du câble de myosine montrent un relâchement de la surface apicale et un recul du noyau. Ainsi, la force émise par les cellules apoptotiques est transmise dans l'axe apico-basal par une liaison adhérence apicale-câble-noyau. Mon travail met en lumière un mécanisme original de génération de force. Ce nouveau mécanisme de force apico-basale pourrait être conservé dans d'autres types cellulaires engagés dans des processus d'invagination au cours de la morphogenèse. Mes résultats montrent également que le noyau joue un rôle nouveau, au-delà de son rôle de protection du génome, en participant activement à la génération d'une force.