Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.

During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires...

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Autores principales:	Atsushi Kuwahara, Hiroshi Sakai, Yuanjiang Xu, Yasuhiro Itoh, Yusuke Hirabayashi, Yukiko Gotoh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12ac6a25b7bb462b87318339e1d1d35d
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spelling	oai:doaj.org-article:12ac6a25b7bb462b87318339e1d1d35d2021-11-18T08:19:01ZTcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.1932-620310.1371/journal.pone.0094408https://doaj.org/article/12ac6a25b7bb462b87318339e1d1d35d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24832538/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood. We now show that the HMG box transcription factor Tcf3 (also known as Tcf7l1) contributes to this mechanism. Tcf3 is highly expressed in undifferentiated NPCs in the mouse neocortex, and its expression is reduced in intermediate neuronal progenitors (INPs) committed to the neuronal fate. We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay. Tcf3 bound to the promoter of the proneural bHLH gene Neurogenin1 (Neurog1) and repressed its expression. Consistent with this, Tcf3 repressed neuronal differentiation and increased the self-renewal activity of NPCs. We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs. Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation.Atsushi KuwaharaHiroshi SakaiYuanjiang XuYasuhiro ItohYusuke HirabayashiYukiko GotohPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e94408 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atsushi Kuwahara Hiroshi Sakai Yuanjiang Xu Yasuhiro Itoh Yusuke Hirabayashi Yukiko Gotoh Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
description	During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood. We now show that the HMG box transcription factor Tcf3 (also known as Tcf7l1) contributes to this mechanism. Tcf3 is highly expressed in undifferentiated NPCs in the mouse neocortex, and its expression is reduced in intermediate neuronal progenitors (INPs) committed to the neuronal fate. We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay. Tcf3 bound to the promoter of the proneural bHLH gene Neurogenin1 (Neurog1) and repressed its expression. Consistent with this, Tcf3 repressed neuronal differentiation and increased the self-renewal activity of NPCs. We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7) and Lef1, positive mediators of Wnt signaling, in NPCs. Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation.
format	article
author	Atsushi Kuwahara Hiroshi Sakai Yuanjiang Xu Yasuhiro Itoh Yusuke Hirabayashi Yukiko Gotoh
author_facet	Atsushi Kuwahara Hiroshi Sakai Yuanjiang Xu Yasuhiro Itoh Yusuke Hirabayashi Yukiko Gotoh
author_sort	Atsushi Kuwahara
title	Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
title_short	Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
title_full	Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
title_fullStr	Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
title_full_unstemmed	Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
title_sort	tcf3 represses wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/12ac6a25b7bb462b87318339e1d1d35d
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Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.

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