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1.
Phys Biol ; 8(6): 066007, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22120059

RESUMO

Embryonic differentiation and morphogenesis require the coordination of the cascades of gene product expression with the morphogenetic sequence of development. The influence of mechanical deformations driven by morphogenetic movements on biochemical activities was recently revealed by the existence of mechanotransduction processes in development, involving both gene transcription and protein behaviour. In the early Drosophila embryo, apical stabilization of Myosin-II leading to mesoderm invagination at the onset of gastrulation was proposed to be triggered in response to the activation of the Fog mechanotransduction pathway by the Snail-dependent active mechanical oscillations of cell apex sizes. Here we simulate the mesoderm as mechanically coupled cells, with pulsatile forces of constriction at the cell level mimicking Snail-dependent active fluctuations of apexes. We define a critical apex diameter triggering active constriction that mimics the activation of the Fog mechanotransduction pathway leading to cell constriction. We find that collective movements trigger the dynamical transition to constriction predicting the experimental dynamics of mesoderm cell apex size decrease with a modulus of contractility four times higher than the passive modulus of elastic deformation of the cells. The contraction wave is activated in a pulsation frequency-dependent process, and propagates at multicellular scales through local cell-cell mechanical interactions. By reproducing the pattern of Snail and Fog gene product protein expression in a simulation of ventral cells, the model phenocopies the pattern of Myo-II apical stabilization, and the dynamic pattern of constriction that initiates along a central sub-domain of the mesoderm. We propose that multicellular mechanical collective effects couple with mechanotransduction biochemical mechanisms to trigger the transition of collective coordinated constriction, through a mechano-genetic process ensuring efficient and regular mesoderm invagination.


Assuntos
Drosophila/embriologia , Mecanotransdução Celular , Mesoderma/citologia , Animais , Padronização Corporal , Simulação por Computador , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/metabolismo , Modelos Biológicos , Miosina Tipo II/genética , Miosina Tipo II/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Nat Commun ; 8: 13883, 2017 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-28112149

RESUMO

Animal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization. To mimic physiological tissue deformation with a cell scale resolution, liposomes containing magnetic nanoparticles are injected into embryonic epithelia and submitted to time-variable forces generated by a linear array of micrometric soft magnets. Periodic magnetically induced deformations quantitatively phenocopy the soft mechanical endogenous snail-dependent apex pulsations, rescue the medio-apical accumulation of Rok, Myo-II and subsequent mesoderm invagination lacking in sna mutants, in a Fog-dependent mechanotransductive process. Mesoderm invagination then activates Myo-II apical accumulation, in a similar Fog-dependent mechanotransductive process, which in turn initiates endoderm invagination. This reveals the existence of a highly dynamic self-inductive cascade of mesoderm and endoderm invaginations, regulated by mechano-induced medio-apical stabilization of Myo-II.


Assuntos
Drosophila melanogaster/embriologia , Embrião não Mamífero/fisiologia , Endoderma/fisiologia , Mecanotransdução Celular/fisiologia , Mesoderma/fisiologia , Miosina Tipo II/metabolismo , Animais , Gastrulação/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Magnetismo , Miosina Tipo II/genética , Interferência de RNA
3.
Nat Commun ; 4: 2821, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24281726

RESUMO

The modulation of developmental biochemical pathways by mechanical cues is an emerging feature of animal development, but its evolutionary origins have not been explored. Here we show that a common mechanosensitive pathway involving ß-catenin specifies early mesodermal identity at gastrulation in zebrafish and Drosophila. Mechanical strains developed by zebrafish epiboly and Drosophila mesoderm invagination trigger the phosphorylation of ß-catenin-tyrosine-667. This leads to the release of ß-catenin into the cytoplasm and nucleus, where it triggers and maintains, respectively, the expression of zebrafish brachyury orthologue notail and of Drosophila Twist, both crucial transcription factors for early mesoderm identity. The role of the ß-catenin mechanosensitive pathway in mesoderm identity has been conserved over the large evolutionary distance separating zebrafish and Drosophila. This suggests mesoderm mechanical induction dating back to at least the last bilaterian common ancestor more than 570 million years ago, the period during which mesoderm is thought to have emerged.


Assuntos
Proteínas do Domínio Armadillo/metabolismo , Evolução Biológica , Proteínas de Drosophila/metabolismo , Mecanotransdução Celular , Mesoderma/fisiologia , Fatores de Transcrição/metabolismo , Proteínas de Peixe-Zebra/metabolismo , beta Catenina/metabolismo , Animais , Sequência Conservada/fisiologia , Drosophila , Feminino , Proteínas Fetais , Masculino , Mecanotransdução Celular/fisiologia , Transdução de Sinais/fisiologia , Proteínas com Domínio T/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Peixe-Zebra
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