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
Cited by
4 articles.
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