再生蛋白是一种对多个细胞过程至关重要的跨膜受体,包括神经发生,星形胶质细胞生成,软骨内骨形成,和铁稳态。在这里,我们提供的证据表明,再生蛋白的丢失有助于持续性增生性原发性玻璃体(PHPV)形成的发病机理,一种遗传性疾病,约占美国失明的5%。神经c细胞中再生蛋白的选择性丢失(如在Wnt1-Cre;Neof/f小鼠中观察到的),但不是神经干细胞(如在GFAP-Cre和Nestin-Cre;Neof/f小鼠中观察到的),导致神经c细胞迁移或分层的失调,表现出PHPV样病理特征(例如,后牙包块升高),未闭合的视网膜裂隙,和小眼症。这些结果表明,再生蛋白在预防PHPV发病机制中具有未被识别的功能,提示再生蛋白调节神经c细胞分层/迁移和视网膜裂隙形成是PHPV的潜在潜在潜在机制。
Neogenin is a transmembrane receptor critical for multiple cellular processes, including neurogenesis, astrogliogenesis, endochondral bone formation, and iron homeostasis. Here we present evidence that loss of neogenin contributes to pathogenesis of persistent hyperplastic primary vitreous (
PHPV) formation, a genetic disorder accounting for ~ 5% of blindness in the USA. Selective loss of neogenin in neural crest cells (as observed in Wnt1-Cre; Neof/f mice), but not neural stem cells (as observed in GFAP-Cre and Nestin-Cre; Neof/f mice), resulted in a dysregulation of neural crest cell migration or delamination, exhibiting features of
PHPV-like pathology (e.g. elevated retrolental mass), unclosed retinal fissure, and microphthalmia. These results demonstrate an unrecognized function of neogenin in preventing
PHPV pathogenesis, implicating neogenin regulation of neural crest cell delamination/migration and retinal fissure formation as potential underlying mechanisms of
PHPV.