RESUMEN
The kinase PAR-4/LKB1 is a major regulator of intestinal homeostasis, which prevents polyposis in humans. Moreover, its ectopic activation is sufficient to induce polarization and formation of microvilli-like structures in intestinal cell lines. Here, we use Caenorhabditis elegans to examine the role of PAR-4 during intestinal development in vivo. We show that it is not required to establish enterocyte polarity and plays only a minor role in brush border formation. By contrast, par-4 mutants display severe deformations of the intestinal lumen as well as supernumerary intestinal cells, thereby revealing a previously unappreciated function of PAR-4 in preventing intestinal hyperplasia. The presence of supernumerary enterocytes in par-4 mutants is not due to excessive cell proliferation, but rather to the abnormal expression of the intestinal cell fate factors end-1 and elt-2 outside the E lineage. Notably, par-4 mutants also display reduced expression of end-1 and elt-2 inside the E lineage. Our work thereby unveils an essential and dual role of PAR-4, which both restricts intestinal specification to the E lineage and ensures its robust differentiation.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Humanos , Caenorhabditis elegans/crecimiento & desarrollo , Proteínas de Caenorhabditis elegans/metabolismo , Polaridad Celular , Endodermo/metabolismo , Hiperplasia/metabolismo , Intestinos , Embrión no Mamífero/metabolismoRESUMEN
Cell shape changes mainly rely on the remodeling of the actin cytoskeleton. Multiciliated cells (MCCs) of the mucociliary epidermis of Xenopus laevis embryos, as they mature, dramatically reshape their apical domain to grow cilia, in coordination with the underlying actin cytoskeleton. Crumbs (Crb) proteins are multifaceted transmembrane apical polarity proteins known to recruit actin linkers and promote apical membrane growth. Here, we identify the homeolog Crb3.L as an important player for the migration of centrioles or basal bodies (collectively centrioles/BBs) and apical domain morphogenesis in MCCs. Crb3.L is present in cytoplasmic vesicles close to the ascending centrioles/BBs, where it partially colocalizes with Rab11a. Crb3.L morpholino-mediated depletion in MCCs caused abnormal migration of centrioles/BBs, a reduction of their apical surface, disorganization of their apical actin meshwork and defective ciliogenesis. Rab11a morpholino-mediated depletion phenocopied Crb3.L loss-of-function in MCCs. Thus, the control of centrioles/BBs migration by Crb3.L might be mediated by Rab11a-dependent apical trafficking. Furthermore, we show that both phospho-activated ERM (pERM; Ezrin-Radixin-Moesin) and Crb3.L are recruited to the growing apical domain of MCCs, where Crb3.L likely anchors pERM, allowing actin-dependent expansion of the apical membrane.
Asunto(s)
Citoesqueleto de Actina , Actinas , Actinas/metabolismo , Morfolinos/metabolismo , Citoesqueleto de Actina/metabolismo , Membrana Celular/metabolismo , Cilios/metabolismoRESUMEN
The intestinal brush border is made of an array of microvilli that increases the membrane surface area for nutrient processing, absorption and host defense. Studies on mammalian cultured epithelial cells have uncovered some of the molecular players and physical constraints required to establish this apical specialized membrane. However, the building and maintenance of a brush border in vivo has not yet been investigated in detail. Here, we combined super-resolution imaging, transmission electron microscopy and genome editing in the developing nematode Caenorhabditis elegans to build a high-resolution and dynamic localization map of known and new brush border markers. Notably, we show that microvilli components are dynamically enriched at the apical membrane during microvilli outgrowth and maturation, but become highly stable once microvilli are built. This new toolbox will be instrumental for understanding the molecular processes of microvilli growth and maintenance in vivo, as well as the effect of genetic perturbations, notably in the context of disorders affecting brush border integrity.
Asunto(s)
Caenorhabditis elegans/metabolismo , Enterocitos/metabolismo , Microvellosidades/metabolismo , Animales , Caenorhabditis elegans/genética , Microvellosidades/genéticaRESUMEN
ERM proteins are conserved regulators of cortical membrane specialization that function as membrane-actin linkers and molecular hubs. The activity of ERM proteins requires a conformational switch from an inactive cytoplasmic form into an active membrane- and actin-bound form, which is thought to be mediated by sequential PIP2 binding and phosphorylation of a conserved C-terminal threonine residue. Here, we use the single Caenorhabditiselegans ERM ortholog, ERM-1, to study the contribution of these regulatory events to ERM activity and tissue formation in vivo Using CRISPR/Cas9-generated erm-1 mutant alleles, we demonstrate that a PIP2-binding site is crucially required for ERM-1 function. By contrast, dynamic regulation of C-terminal T544 phosphorylation is not essential but modulates ERM-1 apical localization and dynamics in a tissue-specific manner, to control cortical actin organization and support lumen formation in epithelial tubes. Our work highlights the dynamic nature of ERM protein regulation during tissue morphogenesis and the importance of C-terminal phosphorylation in fine-tuning ERM activity in a tissue-specific context.
Asunto(s)
Actinas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas del Citoesqueleto/metabolismo , Citoesqueleto de Actina , Secuencia de Aminoácidos , Animales , Sitios de Unión , Caenorhabditis elegans/crecimiento & desarrollo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/genética , Humanos , Mucosa Intestinal/metabolismo , Larva/crecimiento & desarrollo , Larva/metabolismo , Mutagénesis Sitio-Dirigida , Fosforilación , Unión Proteica , Dominios Proteicos , Alineación de SecuenciaRESUMEN
An array detector allows a resolution gain for confocal microscopy by combining images sensed by a set of photomultipliers tubes (or sub-detectors). Several methods have been proposed to reconstruct a high-resolution image by linearly combining sub-detector images, especially the fluorescence emission difference (FED) technique. To improve the resolution and contrast of FED microscopy based on an array detector, we propose to associate sparse denoising with spatial adaptive estimation. We show on both calibration slides and real data that our approach applied to the full stack of spatially reassigned detector signals, enables us to achieve a higher reconstruction performance in terms of resolution, image contrast, and noise reduction.
Asunto(s)
Algoritmos , Microscopía Fluorescente , Microscopía Confocal , CalibraciónRESUMEN
Intestine function relies on the strong polarity of intestinal epithelial cells and the array of microvilli forming a brush border at their luminal pole. Combining a genetic RNA interference (RNAi) screen with in vivo super-resolution imaging in the Caenorhabditiselegans intestine, we found that the V0 sector of the vacuolar ATPase (V0-ATPase) controls a late apical trafficking step, involving Ras-related protein 11 (RAB-11)+ endosomes and the N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) synaptosome-associated protein 29 (SNAP-29), and is necessary to maintain the polarized localization of both apical polarity modules and brush border proteins. We show that the V0-ATPase pathway also genetically interacts with glycosphingolipids and clathrin in enterocyte polarity maintenance. Finally, we demonstrate that silencing of the V0-ATPase fully recapitulates the severe structural, polarity and trafficking defects observed in enterocytes from individuals with microvillus inclusion disease (MVID) and use this new in vivo MVID model to follow the dynamics of microvillus inclusions. Thus, we describe a new function for V0-ATPase in apical trafficking and epithelial polarity maintenance and the promising use of the C. elegans intestine as an in vivo model to better understand the molecular mechanisms of rare genetic enteropathies.
Asunto(s)
Proteínas de Caenorhabditis elegans/fisiología , Polaridad Celular/genética , Enterocitos/fisiología , Mucosa Intestinal/fisiología , ATPasas de Translocación de Protón/fisiología , ATPasas de Translocación de Protón Vacuolares/fisiología , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans , Membrana Celular/metabolismo , Membrana Celular/fisiología , Absorción Intestinal/genética , Mucosa Intestinal/metabolismo , Transporte de Proteínas/genética , Transducción de SeñalRESUMEN
E-cadherin (E-cad) is the main component of epithelial junctions in multicellular organisms, where it is essential for cell-cell adhesion. The localisation of E-cad is often strongly polarised in the apico-basal axis. However, the mechanisms required for its polarised distribution are still largely unknown. We performed a systematic RNAi screen in vivo to identify genes required for the strict E-cad apical localisation in C. elegans epithelial epidermal cells. We found that the loss of clathrin, its adaptor AP-1 and the AP-1 interactor SOAP-1 induced a basolateral localisation of E-cad without affecting the apico-basal diffusion barrier. We further found that SOAP-1 controls AP-1 localisation, and that AP-1 is required for clathrin recruitment. Finally, we also show that AP-1 controls E-cad apical delivery and actin organisation during embryonic elongation, the final morphogenetic step of embryogenesis. We therefore propose that a molecular pathway, containing SOAP-1, AP-1 and clathrin, controls the apical delivery of E-cad and morphogenesis.
Asunto(s)
Proteínas del Dominio Armadillo/metabolismo , Cadherinas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriología , Adhesión Celular/fisiología , Polaridad Celular/fisiología , Desarrollo Embrionario/fisiología , Epidermis/fisiología , Animales , Clatrina/metabolismo , Epidermis/metabolismo , Microscopía Confocal , Microscopía Electrónica , Interferencia de ARN , Factor de Transcripción AP-1/metabolismoRESUMEN
Cryo-sectioning procedures, initially developed by Tokuyasu, have been successfully improved for tissues and cultured cells, enabling efficient protein localization on the ultrastructural level. Without a standard procedure applicable to any sample, currently existing protocols must be individually modified for each model organism or asymmetric sample. Here, we describe our method that enables reproducible cryo-sectioning of Caenorhabditis elegans larvae/adults and embryos. We have established a chemical-fixation procedure in which flat embedding considerably simplifies manipulation and lateral orientation of larvae or adults. To bypass the limitations of chemical fixation, we have improved the hybrid cryo-immobilization-rehydration technique and reduced the overall time required to complete this procedure. Using our procedures, precise cryo-sectioning orientation can be combined with good ultrastructural preservation and efficient immuno-electron microscopy protein localization. Also, GFP fluorescence can be efficiently preserved, permitting a direct correlation of the fluorescent signal and its subcellular localization. Although developed for C. elegans samples, our method addresses the challenge of working with small asymmetric samples in general, and thus could be used to improve the efficiency of immuno-electron localization in other model organisms.
Asunto(s)
Caenorhabditis elegans/ultraestructura , Crioultramicrotomía/métodos , AnimalesRESUMEN
BACKGROUND INFORMATION: Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients. RESULTS: We found that the polarity determinants Cdc42, Par6B, PKCζ/ι and the structural proteins ezrin and phospho-ezrin were lost from the apical membrane and accumulated either in the cytoplasm or on the basal side of enterocytes in patients, which suggests an inversion of cell polarity. Moreover, microvilli-like structures were observed at the basal side as per electron microscopy analysis. We next performed Myo5B depletion in three dimensional grown human Caco2 cells forming cysts and found a direct link between the loss of Myo5B and the mislocalisation of the same apical proteins; furthermore, we observed that a majority of cysts displayed an inverted polarity phenotype as seen in some patients. Finally, we found that this loss of polarity was specific for MVID: tissue samples of patients with Myo5B-independent absorption disorders showed normal polarity but we identified Cdc42 as a potentially essential biomarker for trichohepatoenteric syndrome. CONCLUSION: Our findings indicate that the loss of Myo5B induces a strong loss of enterocyte polarity, potentially leading to polarity inversion. SIGNIFICANCE: Our results show that polarity determinants could be useful markers to help establishing a diagnosis in patients. Furthermore, they could be used to characterise other rare intestinal absorption diseases.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Membrana Celular/metabolismo , Polaridad Celular/fisiología , Síndromes de Malabsorción/metabolismo , Microvellosidades/patología , Mucolipidosis/metabolismo , Proteína de Unión al GTP cdc42/metabolismo , Células CACO-2/metabolismo , Enterocitos/metabolismo , Humanos , Síndromes de Malabsorción/patología , Microvellosidades/metabolismo , Mucolipidosis/patología , Mutación/genética , Cadenas Pesadas de Miosina/metabolismo , Miosina Tipo V/genética , Miosina Tipo V/metabolismo , Transporte de Proteínas/genética , Transporte de Proteínas/fisiologíaRESUMEN
Epithelial tubes perform functions that are essential for the survival of multicellular organisms. Understanding how their polarised features are maintained is therefore crucial. By analysing the function of the clathrin adaptor AP-1 in the C. elegans intestine, we found that AP-1 is required for epithelial polarity maintenance. Depletion of AP-1 subunits does not affect epithelial polarity establishment or the formation of the intestinal lumen. However, the loss of AP-1 affects the polarised distribution of both apical and basolateral transmembrane proteins. Moreover, it triggers de novo formation of ectopic apical lumens between intestinal cells along the lateral membranes later during embryogenesis. We also found that AP-1 is specifically required for the apical localisation of the small GTPase CDC-42 and the polarity determinant PAR-6. Our results demonstrate that AP-1 controls an apical trafficking pathway required for the maintenance of epithelial polarity in vivo in a tubular epithelium.
Asunto(s)
Complejo 1 de Proteína Adaptadora/fisiología , Caenorhabditis elegans/embriología , Polaridad Celular/fisiología , Intestinos/embriología , Complejo 1 de Proteína Adaptadora/metabolismo , Animales , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Intestinos/citología , Microscopía Confocal , Microscopía Electrónica , Transporte de Proteínas/fisiología , Interferencia de ARN , Proteína de Unión al GTP cdc42/metabolismoRESUMEN
We present gene prioritization system (GPSy), a cross-species gene prioritization system that facilitates the arduous but critical task of prioritizing genes for follow-up functional analyses. GPSy's modular design with regard to species, data sets and scoring strategies enables users to formulate queries in a highly flexible manner. Currently, the system encompasses 20 topics related to conserved biological processes including male gamete development discussed in this article. The web server-based tool is freely available at http://gpsy.genouest.org.
Asunto(s)
Genes , Programas Informáticos , Espermatogénesis/genética , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Expresión Génica , Genómica/métodos , Internet , Masculino , Modelos Animales , Anotación de Secuencia Molecular , Interferencia de ARNRESUMEN
Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays a role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function, sin-3 mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) and in vivo imaging, and altered oxygen consumption. Metabolomic analysis of sin-3 mutant animals revealed a mitochondria stress signature and deregulation of methionine flux, resulting in decreased S-adenosyl methionine (SAM) and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.
RESUMEN
Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells. In keeping with impaired myosin VB function, UNC45AKO Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45AKO 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease.
Asunto(s)
Diarrea Infantil , Síndromes de Malabsorción , Mucolipidosis , Miosina Tipo V , Animales , Células CACO-2 , Diarrea Infantil/metabolismo , Diarrea Infantil/patología , Facies , Retardo del Crecimiento Fetal , Enfermedades del Cabello , Humanos , Lactante , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Síndromes de Malabsorción/metabolismo , Microvellosidades/genética , Microvellosidades/patología , Mucolipidosis/genética , Mucolipidosis/metabolismo , Mucolipidosis/patología , Miosina Tipo V/genética , Miosina Tipo V/metabolismo , Fenotipo , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Weibel-Palade bodies are the 1-5 microm long rod-shaped storage organelles of endothelial cells. We have investigated the determinants and functional significance of this shape. We find that the folding of the hemostatic protein von Willebrand's factor (VWF) into tubules underpins the rod-like shape of Weibel-Palade bodies. Further, while the propeptide and the N-terminal domains of mature VWF are sufficient to form tubules, their maintenance relies on a pH-dependent interaction between the two. We show that the tubular conformation of VWF is essential for a rapid unfurling of 100 microm long, platelet-catching VWF filaments when exposed to neutral pH after exocytosis in cell culture and in living blood vessels. If tubules are disassembled prior to exocytosis, then short or tangled filaments are released and platelet recruitment is reduced. Thus, a 100-fold compaction of VWF into tubules determines the unique shape of Weibel-Palade bodies and is critical to this protein's hemostatic function.
Asunto(s)
Endotelio Vascular/metabolismo , Endotelio Vascular/ultraestructura , Cuerpos de Weibel-Palade/metabolismo , Factor de von Willebrand/fisiología , Animales , Secuencia de Bases , Células Cultivadas , ADN/genética , Exocitosis , Hemostasis/fisiología , Humanos , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BL , Monensina/farmacología , Adhesividad Plaquetaria , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Vénulas/efectos de los fármacos , Vénulas/fisiología , Factor de von Willebrand/química , Factor de von Willebrand/genética , Factor de von Willebrand/metabolismoRESUMEN
Current super-resolution microscopy (SRM) methods suffer from an intrinsic complexity that might curtail their routine use in cell biology. We describe here random illumination microscopy (RIM) for live-cell imaging at super-resolutions matching that of 3D structured illumination microscopy, in a robust fashion. Based on speckled illumination and statistical image reconstruction, easy to implement and user-friendly, RIM is unaffected by optical aberrations on the excitation side, linear to brightness, and compatible with multicolor live-cell imaging over extended periods of time. We illustrate the potential of RIM on diverse biological applications, from the mobility of proliferating cell nuclear antigen (PCNA) in U2OS cells and kinetochore dynamics in mitotic S. pombe cells to the 3D motion of myosin minifilaments deep inside Drosophila tissues. RIM's inherent simplicity and extended biological applicability, particularly for imaging at increased depths, could help make SRM accessible to biology laboratories.
Asunto(s)
Procesamiento de Imagen Asistido por Computador , Iluminación , Animales , Microscopía Fluorescente/métodos , DrosophilaRESUMEN
Clathrin provides an external scaffold to form small 50-100-nm transport vesicles. In contrast, formation of much larger dense-cored secretory granules is driven by selective aggregation of internal cargo at the trans-Golgi network; the only known role of clathrin in dense-cored secretory granules formation is to remove missorted proteins by small, coated vesicles during maturation of these spherical organelles. The formation of Weibel-Palade bodies (WPBs) is also cargo driven, but these are cigar-shaped organelles up to 5 mum long. We hypothesized that a cytoplasmic coat might be required to make these very different structures, and we found that new and forming WPBs are extensively, sometimes completely, coated. Overexpression of an AP-180 truncation mutant that prevents clathrin coat formation or reduced AP-1 expression by small interfering RNA both block WPB formation. We propose that, in contrast to other secretory granules, cargo aggregation alone is not sufficient to form immature WPBs and that an external scaffold that contains AP-1 and clathrin is essential.
Asunto(s)
Complejo 1 de Proteína Adaptadora/metabolismo , Vesículas Cubiertas por Clatrina/metabolismo , Células Endoteliales/metabolismo , Cuerpos de Weibel-Palade/metabolismo , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Clatrina/metabolismo , Vesículas Cubiertas por Clatrina/ultraestructura , Células Endoteliales/efectos de los fármacos , Células Endoteliales/ultraestructura , Furina/metabolismo , Humanos , Transporte de Proteínas/efectos de los fármacos , Interferencia de ARN , Acetato de Tetradecanoilforbol/farmacología , Cordón Umbilical/citología , Cordón Umbilical/ultraestructura , Cuerpos de Weibel-Palade/efectos de los fármacos , Cuerpos de Weibel-Palade/ultraestructura , Red trans-Golgi/efectos de los fármacos , Red trans-Golgi/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
Cell-cell signaling is essential for the development of multi-cellular organisms. Indeed, membrane traffic is required for the correct sorting and function of receptors and ligands. In the past decades, many genetic screens performed in C. elegans and Drosophila have been crucial to identify the role of intracellular traffic in signaling. In this review, we discuss recent work that led to the identification of Wntless, a sorting receptor for WNT, and of the retromer, a protein complex required for the recycling of Wntless from endosomes to the trans-Golgi network.
Asunto(s)
Caenorhabditis elegans/fisiología , Transducción de Señal/fisiología , Proteínas Wnt/fisiología , Animales , Proteínas de Caenorhabditis elegans/fisiología , Comunicación Celular/fisiología , Drosophila/fisiología , Proteínas de Drosophila/fisiologíaRESUMEN
Coordinating mitotic spindle and cytokinetic furrow positioning is essential to ensure proper DNA segregation. Here, we present a novel mechanism, which corrects DNA segregation defects due to cytokinetic furrow mispositioning during the first division of C. elegans embryos. Correction of DNA segregation defects due to an abnormally anterior cytokinetic furrow relies on the concomitant and opposite displacements of the furrow and of the anterior nucleus toward the posterior and anterior poles of the embryo, respectively. It also coincides with cortical blebbing and an anteriorly directed cytoplasmic flow. Although microtubules contribute to nuclear displacement, relaxation of an excessive tension at the anterior cortex plays a central role in the correction process and simultaneously regulates cytoplasmic flow as well as nuclear and furrow displacements. This work thus reveals the existence of a so-far uncharacterized correction mechanism, which is critical to correct DNA segregation defects due to cytokinetic furrow mispositioning.
Asunto(s)
Segregación Cromosómica/fisiología , Citocinesis/fisiología , Animales , Fenómenos Biomecánicos/fisiología , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans , Núcleo Celular , ADN , Microtúbulos/fisiología , Mitosis/fisiología , Huso Acromático/fisiologíaRESUMEN
How tissues from different developmental origins interact to achieve coordinated morphogenesis at the level of a whole organism is a fundamental question in developmental biology. While biochemical signaling pathways controlling morphogenesis have been extensively studied [1-3], morphogenesis of epithelial tissues can also be directed by mechanotransduction pathways physically linking two tissues [4-8]. C. elegans embryonic elongation requires the coordination of three tissues: muscles, the dorsal and ventral epidermis, and the lateral epidermis. Elongation starts by cell-shape changes driven by actomyosin contractions in the lateral epidermis [9, 10]. At mid-elongation, muscles become connected to the apical surface of the dorsal and ventral epidermis by molecular tendons formed by muscle integrins, extracellular matrix, and C. elegans hemidesmosomes (CeHDs). The mechanical signal generated by the onset of muscle contractions in the antero-posterior axis from mid-elongation is translated into a biochemical pathway controlling the maturation of CeHDs in the dorsal and ventral epidermis [11]. Consistently, mutations affecting muscle contractions or molecular tendons lead to a mid-elongation arrest [12]. Here, we found that the mechanical force generated by muscle contractions and relayed by molecular tendons is transmitted by adherens junctions to lateral epidermal cells, where it establishes a newly identified bipolar planar polarity of the apical PAR module. The planar polarized PAR module is then required for actin planar organization, thus contributing to the determination of the orientation of cell-shape changes and the elongation axis of the whole embryo. This mechanotransduction pathway is therefore essential to coordinate the morphogenesis of three embryonic tissues.