Abstract:
:Zinc-finger E-box binding homeobox 1 (Zeb1) is a key regulator of epithelial-mesenchymal transition and cancer metastasis. Mutation of ZEB1 is associated with human diseases and defective brain development. Here we show that downregulation of Zeb1 expression in embryonic cortical neural progenitor cells (NPCs) is necessary for proper neuronal differentiation and migration. Overexpression of Zeb1 during neuronal differentiation, when its expression normally declines, blocks NPC lineage progression and disrupts multipolar-to-bipolar transition of differentiating neurons, leading to severe migration defects and subcortical heterotopia bands at postnatal stages. ZEB1 regulates a cohort of genes involved in cell differentiation and migration, including Neurod1 and Pard6b. The interaction between ZEB1 and CTBP2 in the embryonic cerebral cortex is required for ZEB1 to elicit its effect on the multipolar-to-bipolar transition, but not its suppression of Neurod1. These findings provide insights into understanding the complexity of transcriptional regulation during neuronal differentiation.
journal_name
Cell Repjournal_title
Cell reportsauthors
Wang H,Xiao Z,Zheng J,Wu J,Hu XL,Yang X,Shen Qdoi
10.1016/j.celrep.2019.04.081subject
Has Abstractpub_date
2019-05-21 00:00:00pages
2335-2353.e6issue
8issn
2211-1247pii
S2211-1247(19)30561-3journal_volume
27pub_type
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