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首页> 外文期刊>Development >Differential effects of N-cadherin-mediated adhesion on the development of myotomal waves.
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Differential effects of N-cadherin-mediated adhesion on the development of myotomal waves.

机译:N-钙黏着蛋白介导的粘附对肌电波发展的不同作用。

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Myotomal fibers form by a first wave of pioneer myoblasts from the medial epithelial somite, and by a second wave from all four lips of the dermomyotome. Then, a third wave of mitotic progenitors colonizes the myotome, initially stemming from the extreme lips and, later, from the central dermomyotome sheet. In vitro studies have suggested that N-cadherin plays a role in myogenesis, but its role in vivo remains poorly understood. We find that during the growth phase of the dermomyotome sheet, when the orientation of mitotic spindles is parallel to the mediolateral extent of the epithelium, N-cadherin protein is inherited by both daughter cells. Prior to dermomyotome dissociation into dermis and muscle progenitors, when mitoses become perpendicularly oriented, N-cadherin remains associated only with the apical cell located in apposition to the myotome, generating molecular asymmetry between basal and apical progeny. Local gene missexpression confirms that N-cadherin-mediated adhesion is sufficient to promote myotome colonization, whereas its absence drives cells towards the subectodermal domain, hence coupling the asymmetric distribution of N-cadherin to a shift in mitotic orientation and to fate segregation. Site-directed electroporation to additional, discrete somite regions, further reveals that N-cadherin-mediated adhesion is necessary for maintaining the epithelial configuration of all dermomyotome domains while promoting the onset of Myod transcription and the translocation into the myotome of myofibers and/or of Pax-positive progenitors. By contrast, N-cadherin has no effect on migration or differentiation of the first wave of myotomal pioneers. Altogether, we show for the first time that the asymmetric localization of N-cadherin during mitosis indirectly influences fate segregation by differentially driving the allocation of progenitors to muscle versus dermal primordia, that the adhesive domain of N-cadherin maintains the integrity of the dermomyotome epithelium, which is necessary for myogenic specification, and that different molecular mechanisms underlie the establishment of pioneer and later myotomal waves.
机译:肌纤维由来自内侧上皮体的第一波成年先驱成肌细胞,以及来自真皮肌膜刀的所有四个唇的第二波形成。然后,第三波有丝分裂祖细胞定植在肌膜上,最初起源于极端的嘴唇,后来起源于中央的皮肤切开术组。体外研究表明,N-钙粘着蛋白在肌发生中起作用,但其在体内的作用仍知之甚少。我们发现在皮肌膜片的生长阶段,当有丝分裂纺锤体的方向与上皮的中外侧平行时,N-钙粘蛋白被两个子细胞遗传。在皮肌切开术解离为真皮和肌肉祖细胞之前,当有丝分裂成垂直方向时,N-钙粘着蛋白仅与位于与肌成膜节并置的根尖细胞相关,从而在基底和根尖后代之间产生分子不对称性。局部基因的错表达证实,N-钙粘蛋白介导的粘附足以促进肌膜细胞定植,而其缺失会促使细胞向表皮下结构域移动,因此将N-钙粘蛋白的不对称分布与有丝分裂方向的改变和命运的分离联系在一起。定点电穿孔到其他离散的体节区域,进一步揭示了N-钙黏着蛋白介导的粘附对于维持所有皮肤肌球蛋白域的上皮构型,同时促进Myod转录的开始以及肌纤维和/或肌纤维的肌球蛋白的移位是必要的。 Pax阳性祖细胞。相比之下,N-钙粘着蛋白对肌肉先驱者的第一波迁移或分化没有影响。总的来说,我们首次证明有丝分裂过程中N-钙粘着蛋白的不对称定位通过差异驱动祖细胞向肌肉和真皮原基的分配而间接影响命运的分离,N-钙粘着蛋白的黏附域保持了皮肤平滑肌上皮的完整性。 ,这是肌成象规范所必需的,并且先驱和后来的肌成波的建立是不同分子机制的基础。

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