Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS Genet. 2013;9(9):e1003851. doi: 10.1371/journal.pgen.1003851. Epub 2013 Sep 26.
The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.
原始脸由神经嵴细胞 (NCC) 衍生的突起组成。中鼻突 (MNP) 发育形成上唇和犁鼻器,对正常颅面发育至关重要,但 MNP 发育的机制在很大程度上仍不清楚。PDGFRα 信号对于 NCC 发育和颅面形态发生是至关重要的。在这项研究中,我们表明 PDGFRα 通过维持祖细胞神经嵴细胞 (NCC) 的迁移和 MNP 细胞的增殖来维持 MNP 的发育。进一步的研究表明,PI3K/Akt 和 Rac1 信号通路在 MNP 发育过程中介导 PDGFRα 的功能。因此,我们确立了 PDGFRα 作为 MNP 发育的新型调节因子,并在细胞和分子水平上阐明了其下游信号通路的作用。