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1.
Nat Commun ; 11(1): 5476, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127887

RESUMO

The formation of vascular tubes is driven by extensive changes in endothelial cell (EC) shape. Here, we have identified a role of the actin-binding protein, Marcksl1, in modulating the mechanical properties of EC cortex to regulate cell shape and vessel structure during angiogenesis. Increasing and depleting Marcksl1 expression level in vivo results in an increase and decrease, respectively, in EC size and the diameter of microvessels. Furthermore, endothelial overexpression of Marcksl1 induces ectopic blebbing on both apical and basal membranes, during and after lumen formation, that is suppressed by reduced blood flow. High resolution imaging reveals that Marcksl1 promotes the formation of linear actin bundles and decreases actin density at the EC cortex. Our findings demonstrate that a balanced network of linear and branched actin at the EC cortex is essential in conferring cortical integrity to resist the deforming forces of blood flow to regulate vessel structure.


Assuntos
Vasos Sanguíneos/anatomia & histologia , Vasos Sanguíneos/fisiologia , Proteínas de Ligação a Calmodulina/metabolismo , Células Endoteliais/metabolismo , Hemodinâmica/fisiologia , Proteínas dos Microfilamentos/metabolismo , Actinas/metabolismo , Actomiosina/metabolismo , Animais , Animais Geneticamente Modificados , Vasos Sanguíneos/citologia , Proteínas de Ligação a Calmodulina/genética , Células Endoteliais/citologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas dos Microfilamentos/genética , Modelos Animais , Transcriptoma , Peixe-Zebra/embriologia
2.
J R Soc Interface ; 15(144)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29997261

RESUMO

Development is a process precisely coordinated in both space and time. Spatial precision has been quantified in a number of developmental systems, and such data have contributed significantly to our understanding of, for example, morphogen gradient interpretation. However, comparatively little quantitative analysis has been performed on timing and temporal coordination during development. Here, we use Drosophila to explore the temporal robustness of embryonic development within physiologically normal temperatures. We find that development is temporally very precise across a wide range of temperatures in the three Drosophila species investigated. However, we find temperature dependence in the timing of developmental events. A simple model incorporating history dependence can explain the developmental temporal trajectories. Interestingly, history dependence is temperature-specific, with either effective negative or positive feedback at different temperatures. We also find that embryos are surprisingly robust to shifting temperatures during embryogenesis. We further identify differences between tropical and temperate species, potentially due to different mechanisms regulating temporal development that depend on the local environment. Our data show that Drosophila embryonic development is temporally robust across a wide range of temperatures. This robustness shows interesting species-specific differences that are suggestive of different sensitivity to temperature fluctuations between Drosophila species.


Assuntos
Aclimatação/fisiologia , Embrião não Mamífero/embriologia , Desenvolvimento Embrionário/fisiologia , Modelos Biológicos , Animais , Drosophila melanogaster , Especificidade da Espécie
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