BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors

Abstract The lateral ventricles of the adult mammalian brain are lined by a single layer of multiciliated ependymal cells, which generate a flow of cerebrospinal fluid through directional beating of their cilia as well as regulate neurogenesis through interaction with adult neural stem cells. Ependy...

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Autores principales:	Hanae Omiya, Shima Yamaguchi, Tomoyuki Watanabe, Takaaki Kuniya, Yujin Harada, Daichi Kawaguchi, Yukiko Gotoh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8d45cf05f2554c719e7020f38a21d2b0
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spelling	oai:doaj.org-article:8d45cf05f2554c719e7020f38a21d2b02021-12-02T14:12:07ZBMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors10.1038/s41598-020-79610-62045-2322https://doaj.org/article/8d45cf05f2554c719e7020f38a21d2b02021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79610-6https://doaj.org/toc/2045-2322Abstract The lateral ventricles of the adult mammalian brain are lined by a single layer of multiciliated ependymal cells, which generate a flow of cerebrospinal fluid through directional beating of their cilia as well as regulate neurogenesis through interaction with adult neural stem cells. Ependymal cells are derived from a subset of embryonic neural stem-progenitor cells (NPCs, also known as radial glial cells) that becomes postmitotic during the late embryonic stage of development. Members of the Geminin family of transcriptional regulators including GemC1 and Mcidas play key roles in the differentiation of ependymal cells, but it remains largely unclear what extracellular signals regulate these factors and ependymal differentiation during embryonic and early-postnatal development. We now show that the levels of Smad1/5/8 phosphorylation and Id1/4 protein expression—both of which are downstream events of bone morphogenetic protein (BMP) signaling—decline in cells of the ventricular-subventricular zone in the mouse lateral ganglionic eminence in association with ependymal differentiation. Exposure of postnatal NPC cultures to BMP ligands or to a BMP receptor inhibitor suppressed and promoted the emergence of multiciliated ependymal cells, respectively. Moreover, treatment of embryonic NPC cultures with BMP ligands reduced the expression level of the ependymal marker Foxj1 and suppressed the emergence of ependymal-like cells. Finally, BMP ligands reduced the expression levels of Gemc1 and Mcidas in postnatal NPC cultures, whereas the BMP receptor inhibitor increased them. Our results thus implicate BMP signaling in suppression of ependymal differentiation from NPCs through regulation of Gemc1 and Mcidas expression during embryonic and early-postnatal stages of mouse telencephalic development.Hanae OmiyaShima YamaguchiTomoyuki WatanabeTakaaki KuniyaYujin HaradaDaichi KawaguchiYukiko GotohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanae Omiya Shima Yamaguchi Tomoyuki Watanabe Takaaki Kuniya Yujin Harada Daichi Kawaguchi Yukiko Gotoh BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
description	Abstract The lateral ventricles of the adult mammalian brain are lined by a single layer of multiciliated ependymal cells, which generate a flow of cerebrospinal fluid through directional beating of their cilia as well as regulate neurogenesis through interaction with adult neural stem cells. Ependymal cells are derived from a subset of embryonic neural stem-progenitor cells (NPCs, also known as radial glial cells) that becomes postmitotic during the late embryonic stage of development. Members of the Geminin family of transcriptional regulators including GemC1 and Mcidas play key roles in the differentiation of ependymal cells, but it remains largely unclear what extracellular signals regulate these factors and ependymal differentiation during embryonic and early-postnatal development. We now show that the levels of Smad1/5/8 phosphorylation and Id1/4 protein expression—both of which are downstream events of bone morphogenetic protein (BMP) signaling—decline in cells of the ventricular-subventricular zone in the mouse lateral ganglionic eminence in association with ependymal differentiation. Exposure of postnatal NPC cultures to BMP ligands or to a BMP receptor inhibitor suppressed and promoted the emergence of multiciliated ependymal cells, respectively. Moreover, treatment of embryonic NPC cultures with BMP ligands reduced the expression level of the ependymal marker Foxj1 and suppressed the emergence of ependymal-like cells. Finally, BMP ligands reduced the expression levels of Gemc1 and Mcidas in postnatal NPC cultures, whereas the BMP receptor inhibitor increased them. Our results thus implicate BMP signaling in suppression of ependymal differentiation from NPCs through regulation of Gemc1 and Mcidas expression during embryonic and early-postnatal stages of mouse telencephalic development.
format	article
author	Hanae Omiya Shima Yamaguchi Tomoyuki Watanabe Takaaki Kuniya Yujin Harada Daichi Kawaguchi Yukiko Gotoh
author_facet	Hanae Omiya Shima Yamaguchi Tomoyuki Watanabe Takaaki Kuniya Yujin Harada Daichi Kawaguchi Yukiko Gotoh
author_sort	Hanae Omiya
title	BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
title_short	BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
title_full	BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
title_fullStr	BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
title_full_unstemmed	BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
title_sort	bmp signaling suppresses gemc1 expression and ependymal differentiation of mouse telencephalic progenitors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8d45cf05f2554c719e7020f38a21d2b0
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BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors

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