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神经发生将 β-连环蛋白从黏附连接重定向到核内,以促进轴突生长。

Neurogenesis redirects β-catenin from adherens junctions to the nucleus to promote axonal growth.

机构信息

Instituto de Biología Molecular de Barcelona (IBMB-CSIC), Parc Científic de Barcelona, Baldiri Reixac 10-12, Barcelona 08028, Spain.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona 08028, Spain.

出版信息

Development. 2023 Aug 15;150(16). doi: 10.1242/dev.201651. Epub 2023 Aug 24.

Abstract

Here, we show that, in the developing spinal cord, after the early Wnt-mediated Tcf transcription activation that confers dorsal identity to neural stem cells, neurogenesis redirects β-catenin from the adherens junctions to the nucleus to stimulate Tcf-dependent transcription in a Wnt-independent manner. This new β-catenin activity regulates genes implicated in several aspects of contralateral axon growth, including axon guidance and adhesion. Using live imaging of ex-vivo chick neural tube, we showed that the nuclear accumulation of β-catenin and the rise in Tcf-dependent transcription both initiate before the dismantling of the adherens junctions and remain during the axon elongation process. Notably, we demonstrated that β-catenin activity in post-mitotic cells depends on TCF7L2 and is central to spinal commissural axon growth. Together, our results reveal Wnt-independent Tcf/β-catenin regulation of genes that control the growth and guidance of commissural axons in chick spinal cord.

摘要

在这里,我们表明,在发育中的脊髓中,在早期 Wnt 介导的 Tcf 转录激活赋予神经干细胞背侧身份之后,神经发生将β-catenin 从黏着连接重新导向到细胞核,以非 Wnt 依赖的方式刺激 Tcf 依赖性转录。这种新的β-catenin 活性调节与对侧轴突生长的几个方面相关的基因,包括轴突导向和黏附。使用鸡胚神经管的离体活成像,我们表明β-catenin 的核积累和 Tcf 依赖性转录的增加都在黏着连接解体之前开始,并在轴突伸长过程中持续存在。值得注意的是,我们证明了有丝分裂后细胞中的β-catenin 活性依赖于 TCF7L2,并且是脊髓连合轴突生长的核心。总之,我们的结果揭示了 Wnt 非依赖的 Tcf/β-catenin 调节基因,控制鸡胚脊髓中连合轴突的生长和导向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b0e/10482005/6a91f1744317/develop-150-201651-g1.jpg

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