TY - JOUR
T1 - Zbed3 Is Indispensable for Wnt Signaling Regulation of Cortical Layers Formation in Developing Brain
AU - Ruan, Xiangbin
AU - Liu, Gaoao
AU - Zhou, Jiafeng
AU - Chen, Pan
AU - Sun, Changjie
AU - Liu, Wei
AU - Wu, Chao
AU - Hou, Lin
AU - Yin, Bin
AU - Qiang, Boqin
AU - Shu, Pengcheng
AU - Peng, Xiaozhong
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Wnt/β-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/β-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt/β-catenin signaling, colocalizes with β-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/β-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 β-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt/β-catenin signaling regulating neuronal layer fates in the developing brain.
AB - Wnt/β-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/β-catenin in neuronal layer fate determination in the neocortex is still unclear. Here, we report that Zbed3, which is a positive regulator of Wnt/β-catenin signaling, colocalizes with β-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/β-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 β-catenin on neocortex layer formation. Hence, our results demonstrate that Zbed3 is indispensable for Wnt/β-catenin signaling regulating neuronal layer fates in the developing brain.
KW - neocortical development
KW - neural progenitor cells
KW - neuronal fate determination
KW - Wnt/β-catenin signaling
KW - Zbed3
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UR - http://www.scopus.com/inward/citedby.url?scp=85113621352&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhab070
DO - 10.1093/cercor/bhab070
M3 - Article
C2 - 33822906
AN - SCOPUS:85113621352
SN - 1047-3211
VL - 31
SP - 4078
EP - 4091
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 9
ER -