TBR2 antagonizes retinoic acid dependent neuronal differentiation by repressing Zfp423 during corticogenesis

Developmental biology

Lisbeth Flores-Garcia^2,1¹  Luca Massimino^1² 

[1] Departments of Cellular&Molecular Medicine and Medicine, Moores Cancer Center, and Institute for Genomic Medicine, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0644, USA^2;Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy^1

关键词: Cortical development;    TBR2;    ZFP423;   

DOI  :  10.1016/j.ydbio.2017.12.020

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

During cerebral cortex development, neural progenitors are required to elaborate a variety of cell differentiation signals to which they are continuously exposed. RA acid is a potent inducer of neuronal differentiation as it was found to influence cortical development. We report herein that TBR2, a transcription factor specific to Intermediate (Basal) Neural Progenitors (INPs), represses activation of the RA responsive element and expression of RA target genes in cell lines. This repressive action on RA signaling was functionally confirmed by the decrease of RA-mediated neuronal differentiation in neural stem cells stably overexpressing TBR2. In vivo mapping of RA activity in the developing cortex indicated that RA activity is detected in radial glial cells and subsequently downregulated in INPs, revealing a fine cell-type specific regulation of its signaling. Thus, TBR2 might be a molecular player in opposing RA signaling in INPs. Interestingly, this negative regulation is achieved at least in part by directly repressing the critical nuclear RA co-factor ZFP423. Indeed, we found ZFP423 to be expressed in the developing cortex and promote RA-dependent neuronal differentiation. These data indicate that TBR2 contributes to suppressing RA signaling in INPs, thereby enabling them to re-enter the cell cycle and delay neuronal differentiation.

【 授权许可】

CC BY