J Neurosci. 2016 May 25;36(21):5833-49. doi: 10.1523/JNEUROSCI.4487-15.2016.
Huang, Z; Sun, D; Hu, JX; Tang, FL; Lee, DH; Wang, Y; Hu, G; Zhu, XJ; Zhou, J; Mei, L; Xiong, WC
Charlie Norwood Veterans Administration Medical Center, Augusta, Georgia 30912. Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Northeast Normal University, Changchun, Jilin 130024, China. Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. Key Laboratory of Laboratory Medicine (Wenzhou Medical University), Ministry of Education, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China. Medical College of Georgia, Augusta University, Augusta, Georgia 30912. Northeast Normal University, Changchun, Jilin 130024, China.
Neogenin, a DCC (deleted in colorectal cancer) family receptor, is highly expressed in neural stem cells (NSCs). However, its function in NSCs remains to be explored. Here we provide in vitro and in vivo evidence for neogenin's function in NSCs to promote neocortical astrogliogenesis, but not self-renewal or neural differentiation. Mechanistically, neogenin in neocortical NSCs was required for BMP2 activation of YAP (yes associated protein). The active/nuclear YAP stabilized phospho-Smad1/5/8 and was necessary for BMP2 induction of astrocytic differentiation. Deletion of yap in mouse neocortical NSCs caused a similar deficit in neocortical astrogliogenesis as that in neogenin mutant mice. Expression of YAP in neogenin mutant NSCs diminished the astrocytic differentiation deficit in response to BMP2. Together, these results reveal an unrecognized function of neogenin in increasing neocortical astrogliogenesis, and identify a pathway of BMP2-neogenin-YAP-Smad1 for astrocytic differentiation in developing mouse neocortex.
The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.