ID transcription factors regulate the ability of Müller glia to become proliferating neurogenic progenitor-like cells

Author:

Taylor Olivia B.,Patel Snehal P.,Hawthorn Evan C.,El-Hodiri Heithem M.ORCID,Fischer Andy J.ORCID

Abstract

AbstractThe purpose of this study was to investigate how ID transcription factors (TFs) regulate the ability of Müller glia (MG) to reprogram into proliferating MG-derived progenitor cells (MGPCs) in the chick retina. We found thatID1is transiently expressed by maturing MG, whereasID4is upregulated and maintained in maturing MG in embryonic retinas. In mature retinas,ID4was prominently expressed by resting MG, but in response to retinal damageID4was rapidly upregulated and then downregulated in MGPCs. By contrast,ID1, ID2andID3were low in resting MG and then upregulated by MGPCs. Inhibition of ID TFs following retinal damage decreased numbers of proliferating MGPCs. Inhibition of IDs after the proliferation of MGPCs significantly increased numbers of progeny that differentiate as neurons. In damaged or undamaged retinas inhibition of IDs increased levels of p21Cip1in MG. In response to damage or insulin+FGF2 levels ofCDKN1Amessage and p21Cip1protein were decreased, absent in proliferating MGPCs, and elevated in MG returning to a resting phenotype. Inhibition of Notch- or gp130/Jak/Stat-signaling in damaged retinas increased levels of ID4 but not p21Cip1in MG. AlthoughID4is the predominant isoform expressed by MG in the chick retina,id1andid2aare predominantly expressed by resting MG and downregulated in activated MG and MGPCs in zebrafish retinas. We conclude that ID TFs have a significant impact on regulating the responses of MG to retinal damage, controlling the ability of MG to proliferate by regulating levels of p21Cip1, and suppressing the neurogenic potential of MGPCs.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3