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在大脑前叶发育过程中，Fezf2通过Wnt/β-连环蛋白信号通路的局部激活来促进神经元分化。

Fezf2 promotes neuronal differentiation through localised activation of Wnt/β-catenin signalling during forebrain development.

作者信息

Zhang Siwei, Li Jingjing, Lea Robert, Vleminckx Kris, Amaya Enrique

机构信息

The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

Department for Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium.

出版信息

Development. 2014 Dec;141(24):4794-805. doi: 10.1242/dev.115691.

DOI:10.1242/dev.115691
PMID:25468942
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4299278/
Abstract

Brain regionalisation, neuronal subtype diversification and circuit connectivity are crucial events in the establishment of higher cognitive functions. Here we report the requirement for the transcriptional repressor Fezf2 for proper differentiation of neural progenitor cells during the development of the Xenopus forebrain. Depletion of Fezf2 induces apoptosis in postmitotic neural progenitors, with concomitant reduction in forebrain size and neuronal differentiation. Mechanistically, we found that Fezf2 stimulates neuronal differentiation by promoting Wnt/β-catenin signalling in the developing forebrain. In addition, we show that Fezf2 promotes activation of Wnt/β-catenin signalling by repressing the expression of two negative regulators of Wnt signalling, namely lhx2 and lhx9. Our findings suggest that Fezf2 plays an essential role in controlling when and where neuronal differentiation occurs within the developing forebrain and that it does so by promoting local Wnt/β-catenin signalling via a double-repressor model.

摘要

脑区域化、神经元亚型多样化和神经回路连接是建立高级认知功能的关键事件。在此，我们报告了转录抑制因子Fezf2在非洲爪蟾前脑发育过程中对神经祖细胞正常分化的必要性。Fezf2的缺失会诱导有丝分裂后神经祖细胞凋亡，同时前脑大小和神经元分化减少。从机制上讲，我们发现Fezf2通过促进发育中的前脑的Wnt/β-连环蛋白信号传导来刺激神经元分化。此外，我们表明Fezf2通过抑制Wnt信号传导的两个负调节因子lhx2和lhx9的表达来促进Wnt/β-连环蛋白信号传导的激活。我们的研究结果表明，Fezf2在控制发育中的前脑内神经元分化的时间和位置方面起着至关重要的作用，并且它通过双抑制模型促进局部Wnt/β-连环蛋白信号传导来实现这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/62761f9c4912/develop-141-115691-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/aa213babe73f/develop-141-115691-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/40a7508e7adf/develop-141-115691-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/9da09f2dab27/develop-141-115691-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/ba9c0bc3d711/develop-141-115691-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/ba6d00d588d5/develop-141-115691-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/62761f9c4912/develop-141-115691-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/aa213babe73f/develop-141-115691-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/40a7508e7adf/develop-141-115691-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/9da09f2dab27/develop-141-115691-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/ba9c0bc3d711/develop-141-115691-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/ba6d00d588d5/develop-141-115691-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e2a/4299278/62761f9c4912/develop-141-115691-g6.jpg

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