Loss of YAP/TAZ impaired the proliferation and differentiation ability of neural progenitor cells

Abstract

YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are downstream effectors of the Hippo pathway, they activate the expression of transcriptional targets that promote cell growth, cell proliferation, and prevent apoptosis. Here I examined the function of YAP/TAZ in mouse neocortex development through conditional deletion of Yap and Taz by Emx1-Cre. Loss of YAP/TAZ cause the hydrocephalus after birth, leads to aberrant development and dilated ventricle in adult stage, this phenotype can be detected as early as P0. YAP/TAZ are expressed in Sox2+ neural progenitor cells, when YAP/TAZ are deleted, the neuroepithelial cell junctions are disrupted; the numbers of Sox2+ cell and Tbr2+ cell are reduced and the ratio of tbr2/Sox2 is also reduced at E15.5. Results of cell cycle analyzing experiments display YAP/TAZ deletion increased the cell cycle exit. The improperly increased expression of Tuj1+ in progenitor cells in the YAP/TAZ deleted cortex indicates the premature of Sox2+ progenitor cells. Together, our results reveal that YAP/TAZ deletion changed the polarity of neuroepithelial cells, and increased the cell cycle exit, reduced the differentiation of Sox2+ cells into Tbr2+ cells through promoting the premature of Tuj1+ cells. These results define the functions of YAP/TAZ in keeping the cell polarity neural progenitors and ensuring their proliferation and differentiation, and also reveal the roles of YAP/TAZ in developing cortex.