Neogenin-YAP signaling in neocortical astrocytic differentiation

Astrocytes, a major type of glial cells in the mammalian central nervous system (CNS), have a wide variety of physiological functions, including formation of the blood brain barrier, and modulation of synaptic transmission and information processing, and maintenance of CNS homeostasis. The signaling pathway initiated by bone morphogenetic protein (BMP) is critical for astrogliogenesis. However, exactly how this pathway regulates astrogliogenesis remains poorly understood. We have recently provided in vitro and in vivo evidence for neogenin's function in neural stem cells (NSCs) to promote neocortical astrogliogenesis. Neogenin in NSCs as well as astrocytes is required for BMP2 activation of RhoA that promotes YAP (yes-associated protein) nuclear translocation, consequently, YAP interaction with nuclear p-Smad1/5/8, and stabilization of Smad1/5/8 signaling. We have also provided evidence that YAP in NSCs is necessary for neocortical astrogliogenesis, and expression of YAP in neogenin deficient NSCs diminishes the astrogliogenesis deficit. These recent findings identify an unrecognized function of neogenin in promoting neocortical astrogliogenesis, and reveal a pathway of BMP2-neogenin-YAP-Smad1 underlying astrogliogenesis in developing mouse neocortex.