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1.
Cells ; 11(13)2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35805087

RESUMO

Fibronectin is essential for somite formation in the vertebrate embryo. Fibronectin matrix assembly starts as cells emerge from the primitive streak and ingress in the unsegmented presomitic mesoderm (PSM). PSM cells undergo cyclic waves of segmentation clock gene expression, followed by Notch-dependent upregulation of meso1 in the rostral PSM which induces somite cleft formation. However, the relevance of the fibronectin matrix for these molecular processes remains unknown. Here, we assessed the role of the PSM fibronectin matrix in the spatio-temporal regulation of chick embryo somitogenesis by perturbing (1) extracellular fibronectin matrix assembly, (2) integrin-fibronectin binding, (3) Rho-associated protein kinase (ROCK) activity and (4) non-muscle myosin II (NM II) function. We found that integrin-fibronectin engagement and NM II activity are required for cell polarization in the nascent somite. All treatments resulted in defective somitic clefts and significantly perturbed meso1 and segmentation clock gene expression in the PSM. Importantly, inhibition of actomyosin-mediated contractility increased the period of hairy1/hes4 oscillations from 90 to 120 min. Together, our work strongly suggests that the fibronectin-integrin-ROCK-NM II axis regulates segmentation clock dynamics and dictates the spatio-temporal localization of somitic clefts.


Assuntos
Actomiosina , Somitos , Actomiosina/metabolismo , Animais , Relógios Biológicos/fisiologia , Embrião de Galinha , Fibronectinas/metabolismo , Integrinas/metabolismo , Somitos/metabolismo
2.
Dev Cell ; 57(4): 440-450.e7, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-34986324

RESUMO

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies ß3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth.


Assuntos
Axônios/fisiologia , Regeneração Nervosa/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Animais , Axônios/patologia , Modelos Animais de Doenças , Glicosilação , Camundongos , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Coluna Vertebral/fisiopatologia
3.
Dev Dyn ; 245(4): 520-35, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26845241

RESUMO

BACKGROUND: Fibronectin extracellular matrix is essential for embryogenesis. Its assembly is a cell-mediated process where secreted fibronectin dimers bind to integrin receptors on receiving cells, which actively assemble fibronectin into a fibrillar matrix. During development, paracrine communication between tissues is crucial for coordinating morphogenesis, typically being mediated by growth factors and their receptors. Recent reports of situations where fibronectin is produced by one tissue and assembled by another, with implications on tissue morphogenesis, suggest that fibronectin assembly may also be a paracrine communication event in certain contexts. RESULTS: Here we addressed which tissues express fibronectin (Fn1) while also localizing assembled fibronectin matrix and determining the mRNA expression and/or protein distribution pattern of integrins α5 and αV, α chains of the major fibronectin assembly receptors, during early chick and mouse development. We found evidence supporting a paracrine system in fibronectin matrix assembly in several tissues, including immature mesenchymal tissues, components of central and peripheral nervous system and developing muscle. CONCLUSIONS: Thus, similarly to growth factor signaling, fibronectin matrix assembly during early development can be both autocrine and paracrine. We therefore propose that it be considered a cell-cell communication event at the same level and significance as growth factor signaling during embryogenesis.


Assuntos
Comunicação Autócrina/fisiologia , Proteínas Aviárias/metabolismo , Embrião de Mamíferos/embriologia , Desenvolvimento Embrionário/fisiologia , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Comunicação Parácrina/fisiologia , Animais , Embrião de Galinha , Camundongos
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