Esteves de Lima Joana, Bou Akar Reem, Mansour Myriam, Rocancourt Didier, Buckingham Margaret, Relaix Frédéric
Univ Paris Est Creteil, Institut National de la Santé et de la Recherche Médicale (INSERM), EnvA, Etablissement Français du Sang (EFS), Assistance Publique Hopitaux de Paris (AP-HP), Institut Mondor de Recherche Biomedicale (IMRB), Creteil, France.
Department of Developmental and Stem Cell Biology, Institut Pasteur, Paris, France.
Front Cell Dev Biol. 2021 Apr 1;9:652652. doi: 10.3389/fcell.2021.652652. eCollection 2021.
PAX3 belongs to the paired-homeobox family of transcription factors and plays a key role as an upstream regulator of muscle progenitor cells during embryonic development. -mutant embryos display impaired somite development, yet the consequences for myotome formation have not been characterized. The early myotome is formed by PAX3-expressing myogenic cells that delaminate from the dermomyotomal lips and migrate between the dermomyotome and sclerotome where they terminally differentiate. Here we show that in -mutant embryos, myotome formation is impaired, displays a defective basal lamina and the regionalization of the structural protein Desmin is lost. In addition, this phenotype is more severe in embryos combining -null and dominant-negative alleles. We identify the adhesion molecule M-Cadherin as a PAX3 target gene, the expression of which is modulated in the myotome according to gain- and loss-of-function alleles analyzed. Taken together, we identify M-Cadherin as a PAX3-target linked to the formation of the myotome.
PAX3属于转录因子的配对同源框家族，在胚胎发育过程中作为肌肉祖细胞的上游调节因子发挥关键作用。-突变胚胎显示出体节发育受损，但对肌节形成的影响尚未明确。早期肌节由表达PAX3的成肌细胞形成，这些细胞从皮肌膜边缘分层并在皮肌膜和体节之间迁移，在那里它们最终分化。在这里，我们表明，在-突变胚胎中，肌节形成受损，基膜有缺陷，结构蛋白结蛋白的区域化丧失。此外，在结合-无效和显性负等位基因的胚胎中，这种表型更严重。我们确定粘附分子M-钙粘蛋白是一个PAX3靶基因，其表达根据所分析的功能获得和功能丧失等位基因在肌节中受到调节。综上所述，我们确定M-钙粘蛋白是一个与肌节形成相关的PAX3靶标。
