TY - JOUR T1 - Deletion of YAP/TAZ in mouse neocortex impaired the proliferation and differentiation ability of neural progenitor cells JF - bioRxiv DO - 10.1101/296053 SP - 296053 AU - Shanshan Kong Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/04/07/296053.abstract N2 - YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are downstream effectors of the Hippo pathway, to activate the expression of transcriptional targets that promote cell growth, cell proliferation, and prevent apoptosis. Aberrant hyper activation of YAP/TAZ causes tissue overgrowth and tumorigenesis, whereas their inactivation impairs tissue development and regeneration. Here we report the deletion of Yap and Taz by Emx1-Cre in mouse neocortex leads to aberrant development and dilated ventricle in adult stage. The phenotype can be detected as early as P0: the cells in ventricular zone is reduced in DKO cortex. Consisted with this, the numbers of Sox2+ cell and Tbr2+ cell are reduced and the ratio of tbr2/Sox2 is also reduced at E17.5 when Yap/Taz are deleted.Furthermore, the deletion of YAP/TAZ leads to the disrupted the neuroepithelial cell junctions. The result of immunology experiments show that Yap/Taz are highly expressed in the apical surface of neuroepithelials and colocalized with Sox2+ cells in mouse neocortex. Results of BrdU-EdU labeling experiment suggested that the cell cycle exit is increased. Together, our results reveal that Yap/Taz deletion elongated S phase and total cell cycle length, and increased the cell cycle exit ratio, therefore reduced the proliferation ability of progenitor cells. Yap/Taz deletion also reduced the differentiation of Sox2+ cells into Tbr2+ cells through promoting the premature of Sox+ cells. Together, these results suggest that Yap/Taz are essential for epithelial cell proliferation and differentiation, and the deletion can promote hydrocephalus pathogenesis. ER -