RESUMO
Body-axis elongation constitutes a key step in animal development, laying out the final form of the entire animal. It relies on the interplay between intrinsic forces generated by molecular motors1-3, extrinsic forces exerted by adjacent cells4-7 and mechanical resistance forces due to tissue elasticity or friction8-10. Understanding how mechanical forces influence morphogenesis at the cellular and molecular level remains a challenge1. Recent work has outlined how small incremental steps power cell-autonomous epithelial shape changes1-3, which suggests the existence of specific mechanisms that stabilize cell shapes and counteract cell elasticity. Beyond the twofold stage, embryonic elongation in Caenorhabditis elegans is dependent on both muscle activity7 and the epidermis; the tension generated by muscle activity triggers a mechanotransduction pathway in the epidermis that promotes axis elongation7. Here we identify a network that stabilizes cell shapes in C. elegans embryos at a stage that involves non-autonomous mechanical interactions between epithelia and contractile cells. We searched for factors genetically or molecularly interacting with the p21-activating kinase homologue PAK-1 and acting in this pathway, thereby identifying the α-spectrin SPC-1. Combined absence of PAK-1 and SPC-1 induced complete axis retraction, owing to defective epidermal actin stress fibre. Modelling predicts that a mechanical viscoplastic deformation process can account for embryo shape stabilization. Molecular analysis suggests that the cellular basis for viscoplasticity originates from progressive shortening of epidermal microfilaments that are induced by muscle contractions relayed by actin-severing proteins and from formin homology 2 domain-containing protein 1 (FHOD-1) formin bundling. Our work thus identifies an essential molecular lock acting in a developmental ratchet-like process.
Assuntos
Actinas/metabolismo , Padronização Corporal/fisiologia , Caenorhabditis elegans/embriologia , Citoesqueleto de Actina/metabolismo , Animais , Caenorhabditis elegans/citologia , Embrião não Mamífero , Células Epidérmicas/citologiaRESUMO
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
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An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Numerous examples of different phenotypic outcomes in response to varying environmental conditions have been described across phyla, from plants to mammals. Here, we examine the impact of the environment on different developmental traits, focusing in particular on one key environmental variable, nutrient availability. We present advances in our understanding of developmental plasticity in response to food variation using the nematode Caenorhabditis elegans, which provides a near-isogenic context while permitting lab-controlled environments and analysis of wild isolates. We discuss how this model has allowed investigators not only to describe developmental plasticity events at the organismal level but also to zoom in on the tissues involved in translating changes in the environment into a plastic response, as well as the underlying molecular pathways, and sometimes associated changes in behaviour. Lastly, we also discuss how early life starvation experiences can be logged to later impact adult physiological traits, and how such memory could be wired.
Assuntos
Caenorhabditis elegans , Alimentos , Animais , Humanos , Nutrientes , Fenótipo , Pesquisadores , MamíferosRESUMO
C. elegans embryonic elongation is a morphogenetic event driven by actomyosin contractility and muscle-induced tension transmitted through hemidesmosomes. A role for the microtubule cytoskeleton has also been proposed, but its contribution remains poorly characterized. Here, we investigate the organization of the non-centrosomal microtubule arrays present in the epidermis and assess their function in elongation. We show that the microtubule regulators γ-tubulin and NOCA-1 are recruited to hemidesmosomes and adherens junctions early in elongation. Several parallel approaches suggest that microtubule nucleation occurs from these sites. Disrupting the epidermal microtubule array by overexpressing the microtubule-severing protein Spastin or by inhibiting the C. elegans ninein homolog NOCA-1 in the epidermis mildly affected elongation. However, microtubules were essential for elongation when hemidesmosomes or the activity of the Rho kinase LET-502/ROCK were partially compromised. Imaging of junctional components and genetic analyses suggest that epidermal microtubules function together with Rho kinase to promote the transport of E-cadherin to adherens junctions and myotactin to hemidesmosomes. Our results indicate that the role of LET-502 in junctional remodeling is likely to be independent of its established function as a myosin II activator, but requires a microtubule-dependent pathway involving the syntaxin SYX-5. Hence, we propose that non-centrosomal microtubules organized by epidermal junctions contribute to elongation by transporting junction remodeling factors, rather than having a mechanical role.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Células Epidérmicas , Microtúbulos/metabolismo , Quinases Associadas a rho/metabolismo , Actomiosina/metabolismo , Junções Aderentes/metabolismo , Animais , Caderinas/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas do Citoesqueleto , Citoesqueleto/metabolismo , Epiderme/metabolismo , Hemidesmossomos/metabolismo , Morfogênese/fisiologia , Proteínas Musculares/metabolismo , Miosina Tipo II/metabolismo , Proteínas Nucleares , Transporte Proteico/genética , Proteínas Qa-SNARE/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Tubulina (Proteína)/metabolismoRESUMO
The microtubule cytoskeleton has a dual contribution to cell organization. First, microtubules help displace chromosomes and provide tracks for organelle transport. Second, microtubule rigidity confers specific mechanical properties to cells, which are crucial in cilia or mechanosensory structures. Here we review the recently uncovered organization and functions of noncentrosomal microtubules in C. elegans epithelia, focusing on how they contribute to nuclear positioning and protein transport. In addition, we describe recent data illustrating how the microtubule and actin cytoskeletons interact to achieve those functions.
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Caenorhabditis elegans/citologia , Epitélio/metabolismo , Microtúbulos/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Transporte ProteicoRESUMO
Neurons require precise targeting of their axons to form a connected network and a functional nervous system. Although many guidance receptors have been identified, much less is known about how these receptors signal to direct growth cone migration. We used Caenorhabditis elegans motoneurons to study growth cone directional migration in response to a repellent UNC-6 (netrin homolog) guidance cue. The evolutionarily conserved kinase MIG-15 [homolog of Nck-interacting kinase (NIK)] regulates motoneuron UNC-6-dependent repulsion through unknown mechanisms. Using genetics and live imaging techniques, we show that motoneuron commissural axon morphology defects in mig-15 mutants result from impaired growth cone motility and subsequent failure to migrate across longitudinal obstacles or retract extra processes. To identify new genes acting with mig-15, we screened for genetic enhancers of the mig-15 commissural phenotype and identified the ezrin/radixin/moesin ortholog ERM-1, the kinesin-1 motor UNC-116 and the actin regulator WVE-1 complex. Genetic analysis indicates that mig-15 and erm-1 act in the same genetic pathway to regulate growth cone migration and that this pathway functions in parallel to the UNC-116/WVE-1 pathway. Further, time-lapse imaging of growth cones in mutants suggests that UNC-116 might be required to stimulate protrusive activity at the leading edge, whereas MIG-15 and ERM-1 maintain low activity at the rear edge. Together, these results support a model in which the MIG-15 kinase and the UNC-116-WVE-1 complex act on opposite sides of the growth cone to promote robust directional migration.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Cones de Crescimento/metabolismo , Cinesinas/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Movimento Celular/fisiologia , Polaridade Celular , Proteínas do Citoesqueleto/genética , Genes de Helmintos , Cinesinas/genética , Neurônios Motores/metabolismo , Mutação , Neurogênese/genética , Neurogênese/fisiologia , Interferência de RNARESUMO
Caenorhabditis elegans embryonic elongation depends on both epidermal and muscle cells. The hemidesmosome-like junctions, commonly called fibrous organelles (FOs), that attach the epidermis to the extracellular matrix ensure muscle anchoring to the cuticular exoskeleton and play an essential role during elongation. To further define how hemidesmosomes might control elongation, we searched for factors interacting with the core hemidesmosome component, the spectraplakin homolog VAB-10. Using the VAB-10 plakin domain as bait in a yeast two-hybrid screen, we identified the novel protein T17H7.4. We also identified T17H7.4 in an independent bioinformatic search for essential nematode-specific proteins that could define novel anti-nematode drug or vaccine targets. Interestingly, T17H7.4 corresponds to the C. elegans equivalent of the parasitic OvB20 antigen, and has a characteristic hemidesmosome distribution. We identified two mutations in T17H7.4, one of which defines the uncharacterized gene pat-12, previously identified in screens for genes required for muscle assembly. Using isoform-specific GFP constructs, we showed that one pat-12 isoform with a hemidesmosome distribution can rescue a pat-12 null allele. We further found that lack of pat-12 affects hemidesmosome integrity, with marked defects at the apical membrane. PAT-12 defines a novel component of C. elegans hemidesmosomes, which is required for maintaining their integrity. We suggest that PAT-12 helps maintaining VAB-10 attachment with matrix receptors.
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Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/embriologia , Hemidesmossomos/fisiologia , Morfogênese , Animais , Antinematódeos , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Proteínas de Caenorhabditis elegans/genética , Células HeLa , Humanos , Biogênese de Organelas , Organelas/fisiologiaRESUMO
Myosin II plays a central role in epithelial morphogenesis; however, its role has mainly been examined in processes involving a single cell type. Here we analyze the structure, spatial requirement and regulation of myosin II during C. elegans embryonic elongation, a process that involves distinct epidermal cells and muscles. We developed novel GFP probes to visualize the dynamics of actomyosin remodeling, and found that the assembly of myosin II filaments, but not actin microfilaments, depends on the myosin regulatory light chain (MLC-4) and essential light chain (MLC-5, which we identified herein). To determine how myosin II regulates embryonic elongation, we rescued mlc-4 mutants with various constructs and found that MLC-4 is essential in a subset of epidermal cells. We show that phosphorylation of two evolutionary conserved MLC-4 serine and threonine residues is important for myosin II activity and organization. Finally, in an RNAi screen for potential myosin regulatory light chain kinases, we found that the ROCK, PAK and MRCK homologs act redundantly. The combined loss of ROCK and PAK, or ROCK and MRCK, completely prevented embryonic elongation, but a constitutively active form of MLC-4 could only rescue a lack of MRCK. This result, together with systematic genetic epistasis tests with a myosin phosphatase mutation, suggests that ROCK and MRCK regulate MLC-4 and the myosin phosphatase. Moreover, we suggest that ROCK and PAK regulate at least one other target essential for elongation, in addition to MLC-4.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans , Morfogênese/fisiologia , Miosina Tipo II/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Quinases Ativadas por p21/metabolismo , Quinases Associadas a rho/metabolismo , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/anatomia & histologia , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Citoesqueleto/metabolismo , Humanos , Dados de Sequência Molecular , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/metabolismo , Miosina Tipo II/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência , Transgenes , Quinases Ativadas por p21/genética , Quinases Associadas a rho/genéticaRESUMO
Transdifferentiation, or direct cell reprogramming, is the conversion of one fully differentiated cell type into another. Whether core mechanisms are shared between natural transdifferentiation events when occurring with or without cell division is unclear. We have previously characterized the Y-to-PDA natural transdifferentiation in Caenorhabditis elegans, which occurs without cell division and requires orthologs of vertebrate reprogramming factors. Here, we identify a rectal-to-GABAergic transdifferentiation and show that cell division is required but not sufficient for conversion. We find shared mechanisms, including erasure of the initial identity, which requires the conserved reprogramming factors SEM-4/SALL, SOX-2, CEH-6/OCT, and EGL-5/HOX. We also find three additional and parallel roles of the Wnt signaling pathway: selection of a specific daughter, removal of the initial identity, and imposition of the precise final subtype identity. Our results support a model in which levels and antagonistic activities of SOX-2 and Wnt signaling provide a timer for the acquisition of final identity.
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Proteínas de Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Transdiferenciação Celular , Mitose , Via de Sinalização WntRESUMO
Epithelial cells play a central role in many embryonic morphogenetic processes, during which they undergo highly coordinated cell shape changes. Here, we review some common principles that have recently emerged through genetic and cellular analyses performed mainly with invertebrate genetic models, focusing on morphogenetic processes involving epithelial sheets. All available data argue that myosin II is the main motor that induces cell shape changes during morphogenesis. We discuss the control of myosin II activity during epithelial morphogenesis, as well as the recently described involvement of microtubules in this process. Finally, we examine how forces unleashed by myosin II can be measured, how embryos use specific brakes to control molecular motors and the potential input of mechano-sensation in morphogenesis.
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Embrião não Mamífero/citologia , Embrião não Mamífero/embriologia , Epitélio/embriologia , Proteínas Motores Moleculares/fisiologia , Morfogênese/fisiologia , Animais , Células Epiteliais/citologia , Células Epiteliais/fisiologiaRESUMO
Clustering neurotransmitter receptors at the synapse is crucial for efficient neurotransmission. Here we identify a Caenorhabditis elegans locus, lev-10, required for postsynaptic aggregation of ionotropic acetylcholine receptors (AChRs). lev-10 mutants were identified on the basis of weak resistance to the anthelminthic drug levamisole, a nematode-specific cholinergic agonist that activates AChRs present at neuromuscular junctions (NMJs) resulting in muscle hypercontraction and death at high concentrations. In lev-10 mutants, the density of levamisole-sensitive AChRs at NMJs is markedly reduced, yet the number of functional AChRs present at the muscle cell surface remains unchanged. LEV-10 is a transmembrane protein localized to cholinergic NMJs and required in body-wall muscles for AChR clustering. We also show that the LEV-10 extracellular region, containing five predicted CUB domains and one LDLa domain, is sufficient to rescue AChR aggregation in lev-10 mutants. This suggests a mechanism for AChR clustering that relies on extracellular protein-protein interactions. Such a mechanism is likely to be evolutionarily conserved because CUB/LDL transmembrane proteins similar to LEV-10, but lacking any assigned function, are expressed in the mammalian nervous system and might be used to cluster ionotropic receptors in vertebrates.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteínas de Membrana/metabolismo , Receptores Colinérgicos/metabolismo , Proteínas de Transporte Vesicular , Animais , Antinematódeos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte/metabolismo , Clonagem Molecular , Relação Dose-Resposta a Droga , Resistência a Medicamentos/efeitos dos fármacos , Éxons/genética , Regulação da Expressão Gênica , Levamisol/farmacologia , Proteínas de Membrana/química , Proteínas de Membrana/genética , Dados de Sequência Molecular , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Mutação/genética , Fenótipo , Estrutura Terciária de Proteína , Transporte Proteico , Sinapses/metabolismo , Proteínas Vesiculares de Transporte de AcetilcolinaRESUMO
The WAVE/SCAR complex promotes actin nucleation through the Arp2/3 complex, in response to Rac signaling. We show that loss of WVE-1/GEX-1, the only C. elegans WAVE/SCAR homolog, by genetic mutation or by RNAi, has the same phenotype as loss of GEX-2/Sra1/p140/PIR121, GEX-3/NAP1/HEM2/KETTE, or ABI-1/ABI, the three other components of the C. elegans WAVE/SCAR complex. We find that the entire WAVE/SCAR complex promotes actin-dependent events at different times and in different tissues during development. During C. elegans embryogenesis loss of CED-10/Rac1, WAVE/SCAR complex components, or Arp2/3 blocks epidermal cell migrations despite correct epidermal cell differentiation. 4D movies show that this failure occurs due to decreased membrane dynamics in specific epidermal cells. Unlike myoblasts in Drosophila, epidermal cell fusions in C. elegans can occur in the absence of WAVE/SCAR or Arp2/3. Instead we find that subcellular enrichment of F-actin in epithelial tissues requires the Rac-WAVE/SCAR-Arp2/3 pathway. Intriguingly, we find that at the same stage of development both F-actin and WAVE/SCAR proteins are enriched apically in one epithelial tissue and basolaterally in another. We propose that temporally and spatially regulated actin nucleation by the Rac-WAVE/SCAR-Arp2/3 pathway is required for epithelial cell organization and movements during morphogenesis.
Assuntos
Actinas/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Movimento Celular , Epitélio/embriologia , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Polaridade Celular , Clonagem Molecular , Embrião não Mamífero/embriologia , Epitélio/metabolismo , Interpretação de Imagem Assistida por Computador , Mucosa Intestinal/metabolismo , Intestinos/embriologia , Morfogênese , Mutação , Fenótipo , Interferência de RNARESUMO
Intermediate filaments (IFs) are involved in multiple cellular processes that are essential for the maintenance of cell and tissue integrity. To achieve this crucial function, IFs have to be organized as long and resistant filaments across the cells and to be tightly anchored at the cell periphery. This anchoring takes place at the level desmosomes and hemidesmosomes through proteins belonging to the spectraplakin family. Here, we focus on the sole nematode Caenorhabditis elegans spectraplakin locus vab-10 that is essential to connect the epidermis to the cuticle apically and to the muscles basally. After briefly reviewing the structure of the gene, we first present the genetic tools available to study this gene as well as the reagents to examine the distribution of its translation products. We discuss the functional assays that enable examining their function. Finally, we detail a genetic method to identify spectraplakin functional partners through RNAi screens, and a biochemical method to examine the phosphorylation status of IFs.
Assuntos
Proteínas de Caenorhabditis elegans/genética , Animais , Sequência de Bases , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/fisiologia , Éxons , Mutação , Estrutura Terciária de ProteínaRESUMO
At GABAergic synapses, GABA receptors form high-density clusters opposite GABA release sites. Whether GABA release per se plays a role in the formation of GABA receptor clusters remains uncertain. To address this question in vivo, we characterized GABA receptor clustering in the nematode Caenorhabditis elegans. In C. elegans, body wall muscles receive excitatory inputs from cholinergic motor neurons and inhibitory inputs from GABAergic neurons. Using immunohistochemistry and green fluorescent protein-tagged proteins, we observed that the muscle GABA receptor UNC-49 is precisely clustered opposite GABA release sites. During development, these clusters appear slightly after the detection of presynaptic vesicles. If motor axons are mislocalized as in unc-5 mutants, GABA receptors cluster opposite ectopic axons at GABA release sites. Together, these data imply that a motor neuron-derived factor is instructing GABA receptor clustering. Presynaptic localization of this clustering activity requires the neuronal kinesin UNC-104, suggesting that release of GABA from synaptic vesicles may represent the clustering signal. However, unc-25 mutants do not synthesize GABA but do cluster postsynaptic GABA receptors indistinguishably from the wild type. Therefore, at GABAergic neuromuscular junctions, GABA receptor clustering requires nerve-muscle interaction but not GABA neurotransmission.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/química , Junção Neuromuscular/química , Receptores de GABA/análise , Ácido gama-Aminobutírico/fisiologia , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/crescimento & desenvolvimento , Diferenciação Celular , Cinesinas/fisiologia , Cinética , Neurônios Motores/fisiologia , Músculos/inervação , Proteínas do Tecido Nervoso/fisiologia , Junção Neuromuscular/crescimento & desenvolvimento , Junção Neuromuscular/fisiologia , Junção Neuromuscular/ultraestrutura , Transporte Proteico , Transmissão SinápticaRESUMO
In Drosophila, relocation of a euchromatic gene near centromeric or telomeric heterochromatin often leads to its mosaic silencing. Nevertheless, modifiers of centromeric silencing do not affect telomeric silencing, suggesting that each location requires specific factors. Previous studies suggest that a subset of Polycomb-group (PcG) proteins could be responsible for telomeric silencing. Here, we present the effect on telomeric silencing of 50 mutant alleles of the PcG genes and of their counteracting trithorax-group genes. Several combinations of two mutated PcG genes impair telomeric silencing synergistically, revealing that some of these genes are required for telomeric silencing. In situ hybridization and immunostaining experiments on polytene chromosomes revealed a strict correlation between the presence of PcG proteins and that of heterochromatic telomeric associated sequences (TASs), suggesting that TASs and PcG complexes could be associated at telomeres. Furthermore, lines harboring a transgene containing an X-linked TAS subunit and the mini-white reporter gene can exhibit pairing-sensitive repression of the white gene in an orientation-dependent manner. Finally, an additional binding site for PcG proteins was detected at the insertion site of this type of transgene. Taken together, these results demonstrate that PcG proteins bind TASs in vivo and may be major players in Drosophila telomeric position effect (TPE).
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Proteínas de Drosophila/metabolismo , Drosophila/genética , Regulação da Expressão Gênica , Telômero , Fatores de Transcrição , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/genética , Genes Reporter , Complexo Repressor Polycomb 1RESUMO
The human brain contains 100 billion neurons and probably one thousand times more synapses. Such a system can be analyzed at different complexity levels, from cognitive functions to molecular structure of ion channels. However, it remains extremely difficult to establish links between these different levels. An alternative strategy relies on the use of much simpler animals that can be easily manipulated. In 1974, S. Brenner introduced the nematode Caenorhabditis elegans as a model system. This worm has a simple nervous system that only contains 302 neurons and about 7,000 synapses. Forward genetic screens are powerful tools to identify genes required for specific neuron functions and behaviors. Moreover, studies of mutant phenotypes can identify the function of a protein in the nervous system. The data that have been obtained in C. elegans demonstrate a fascinating conservation of the molecular and cellular biology of the neuron between worms and mammals through more than 550 million years of evolution.
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Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Modelos Animais , Fenômenos Fisiológicos do Sistema Nervoso , Neurônios/fisiologia , Animais , Evolução Biológica , Regulação da Expressão Gênica , Humanos , Mamíferos , Neurônios Motores/fisiologia , Mutação , Fenótipo , Transmissão Sináptica/fisiologiaRESUMO
Genetic analysis in model organisms has recently achieved a detailed molecular description of many key cellular processes controlling embryonic morphogenesis. To understand higher order tissue morphogenesis, we now need to define how these processes become integrated across different cell groups and cell layers. Here, we review progress in this fast moving area, which was to a large degree made possible by novel imaging methods and the increasingly frequent use of modeling. Discussing examples from Caenorhabditis elegans and Drosophila embryos, two powerful and simple models, we highlight novel principles relying in part on mechanical tension, and outline the role of junctions as signal integrators.