Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states

Abstract Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal proge...

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Autores principales:	Xueqing Chen, Mark M. Emerson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7619a49ad38c47f59e5abf5ba2cd289d
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spelling	oai:doaj.org-article:7619a49ad38c47f59e5abf5ba2cd289d2021-12-02T18:30:45ZNotch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states10.1038/s41598-021-93692-w2045-2322https://doaj.org/article/7619a49ad38c47f59e5abf5ba2cd289d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93692-whttps://doaj.org/toc/2045-2322Abstract Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized inhibition of Notch signaling in restricted progenitor cells does not alter the number of cones derived from these cells. Cell cycle promotion is not a primary effect of Notch signaling but an indirect effect on progenitor cell state transitions that leads to depletion of the multipotent progenitor cell population. Taken together, this suggests that the role of Notch signaling in cone photoreceptor formation and proliferation are both mediated by a localized function of Notch in multipotent retinal progenitor cells to repress the formation of restricted progenitor cells.Xueqing ChenMark M. EmersonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xueqing Chen Mark M. Emerson Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
description	Abstract Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized inhibition of Notch signaling in restricted progenitor cells does not alter the number of cones derived from these cells. Cell cycle promotion is not a primary effect of Notch signaling but an indirect effect on progenitor cell state transitions that leads to depletion of the multipotent progenitor cell population. Taken together, this suggests that the role of Notch signaling in cone photoreceptor formation and proliferation are both mediated by a localized function of Notch in multipotent retinal progenitor cells to repress the formation of restricted progenitor cells.
format	article
author	Xueqing Chen Mark M. Emerson
author_facet	Xueqing Chen Mark M. Emerson
author_sort	Xueqing Chen
title	Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
title_short	Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
title_full	Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
title_fullStr	Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
title_full_unstemmed	Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
title_sort	notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7619a49ad38c47f59e5abf5ba2cd289d
work_keys_str_mv	AT xueqingchen notchsignalingrepressesconephotoreceptorformationthroughtheregulationofretinalprogenitorcellstates AT markmemerson notchsignalingrepressesconephotoreceptorformationthroughtheregulationofretinalprogenitorcellstates
_version_	1718377986095316992

Notch signaling represses cone photoreceptor formation through the regulation of retinal progenitor cell states

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