神经嵴细胞中 Neogenin 的缺失导致永存性原始玻璃体增生症的形成。
Neogenin-loss in neural crest cells results in persistent hyperplastic primary vitreous formation.
机构信息
Department of Neuroscience & Regenerative Medicine and Department of Neurology, Augusta University, Augusta, GA 30912, USA.
Department of Ophthalmology, Daping Hospital, Army Medical Center of PLA, Chongqing, China.
出版信息
J Mol Cell Biol. 2020 Jan 22;12(1):17-31. doi: 10.1093/jmcb/mjz076.
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.
Neogenin 是一种对多种细胞过程至关重要的跨膜受体，包括神经发生、星形胶质细胞发生、软骨内骨形成和铁稳态。在这里，我们提供的证据表明，Neogenin 的缺失导致永存性原始玻璃体增生症 (PHPV)形成的发病机制，这是一种遗传疾病，占美国失明的约 5%。神经嵴细胞（如 Wnt1-Cre；Neof/f 小鼠中观察到的）中 Neogenin 的选择性缺失，但不是神经干细胞（如 GFAP-Cre 和 Nestin-Cre；Neof/f 小鼠中观察到的），导致神经嵴细胞迁移或分层的失调，表现出 PHPV 样病变的特征（例如，视网膜后肿块升高）、视网膜裂未闭合和小眼症。这些结果表明 Neogenin 在预防 PHPV 发病机制中具有未被认识的功能，提示 Neogenin 调节神经嵴细胞分层/迁移和视网膜裂形成可能是 PHPV 的潜在潜在机制。
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