TAZ Modulates Generation Of Cortical Neurons Via Regulating Cell Cycle Length Of Radial Glial Cells In The Developing Cerebral Cortex

Objective The mammalian cortex is a multilaminar structure consisting of distinct layer-specific cortical neurons. These neurons are generated from neural progenitor cells by asymmetric division following a precise temporal sequence and spatial sequence: early-born neurons settle in deep cortical layers whereas late-born neurons populate more superficial layers, formed an “inside-out” neuronal distribution pattern. However, The complex molecular mechanisms underlying the development of the cerebral cortex are not fully understood. Transcriptional coactivator with PDZ-binding motif(TAZ) is associated with stem cell differentiation and organ formation by affecting cell proliferation, differentiation and apoptosis. This article is mainly to investigate the function of TAZ in the development of the cerebral cortex. Methods1、Analysis of the expression of TAZ in the developing cerebral cortex by immunofluorescence staining and Western blotting in the brain tissue of C57 mice collected(at E12, E14, E16, E18) and P0. 2、Analysis of the numbers of radial glial cells(RGCs) and intermediate progenitor cells(IPCs) by immunofluorescence staining. 3、Analysis of proliferation of IPCs and RGCs by Brd U pulse chase analysis and staining for Ki67 and PH3. 4、Analysis of the cell cycle exit and the length of S phase by staining for Brd U and Ki67. 5、alysis of the brain volume and the numbers of distinct layers of cortical neurons by immunofluorescence staining.Results 1、TAZ is expressed by RGCs and cortical neurons and exhibits dynamic expression levels in the developing cerebral cortex. 2、Deficiency of TAZ decreases brain volume. 3、Deficiency of TAZ increases the numbers of RGCs in the VZ. 4、Deficiency of TAZ promotes the proliferation of RGCs by increases the length of S phase of the cell cycle and decreases cell cycle exit. 5、Deficiency of TAZ delays the production of deep-layer cortical neurons.Conclusion TAZ modulates the generation of deep-layer cortical neurons through regulating the cell cycle of RGCs in the developing cerebral cortex.