期刊
CEREBRAL CORTEX
卷 31, 期 9, 页码 4078-4091出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhab070
关键词
neocortical development; neural progenitor cells; neuronal fate determination; Wnt/beta-catenin signaling; Zbed3
资金
- National Natural Science Foundation of China [31970772]
- National Key Research and Development Program of China [2016YFA0100702, 2016YFC0902502]
- CAMS Innovation Fund for Medical Sciences(CIFMS) [2016-I2M-2-001, 2016-I2M-1-004, 2017-I2M-1-004]
The study revealed the important role of Zbed3 in regulating neuronal layer fates during brain development. Overexpression of Zbed3 increased the generation of deep-layer neurons, while its knockdown shifted neuronal fates from deep layers to upper layers.
Wnt/beta-catenin signaling plays multiple important roles during mammalian brain development, and it regulates the proliferation and differentiation of neural progenitors in a context-dependent manner and affects neocortex layer formation. However, the specific role of Wnt/beta-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt/beta-catenin signaling, colocalizes with beta-catenin at the endfeet of radial glia in the ventricular zone of embryo mouse neocortex. Overexpression and knockdown of Zbed3 increased and decreased the activity of Wnt/beta-catenin signaling in the neocortex, respectively. Interestingly, knockdown of Zbed3 in vivo could significantly shift neuronal fates from deep layers to upper layers but is not required for the proliferation and differentiation of neural progenitors. Overexpression of Zbed3 led to increased generation of deep-layer neurons without impairing cell cycle exit of neural progenitors. More importantly, knockdown of Zbed3 could effectively block the effects of the ectopic expression of stabilized beta-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt/beta-catenin signaling regulating neuronal layer fates in the developing brain.
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