Biology subjects

Desai, O. M.

Publications and source records attributed to Desai, O. M..

2 recordsLinked to original sources

bioRxiv2025

YY1 protein is essential for the promotion of Muller glia reprogramming and retina regeneration

Unlike mammals, the Muller glia reprogramming in zebrafish retina restores vision after an acute retinal injury. Here, we explored the Ying yang (Yy1) protein and its multi-faceted roles in different phases of retina regeneration. We show that the acetylation and deacetylation status of Yy1 contribute to its transcriptional activation and repression functions on various target genes, including regeneration-associated genes (RAGs). Yy1 is regulated positively by TGF-{beta} and negatively through Delta-Notch signaling in the injured retina. Yy1-knockdown caused reduced retinal progenitor induction and regeneration, while the opposite was seen in its overexpression. Yy1 collaborates with histone deacetylases, BAF complex, and the effector of TGF-{beta} signaling, pSMAD3, to target the genome differentially. Lastly, the whole transcriptome analysis of the Yy1-debilitated retina revealed differential expression of various RAGs and BMP-signaling. Yy1 facilitates the BMP pathways genes through the downregulation of noggin3. Our study unravels how a single transcription factor, Yy1, could influence many important regulatory steps of retina regeneration.

cell biology↗

bioRxiv2025

Regulation of the lncRNA malat1/Egr1 Axis by Wnt, Notch and TGF-β signaling: A Key Mechanism in Retina Regeneration

Adult zebrafish retinas rely on the resident Muller glia to maintain homeostasis and enable regeneration. Retina regeneration remains incomplete in mammals despite extensive efforts to emulate zebrafish regenerative conditions. Many studies have examined the reprogramming of zebrafish Muller glia cells, which is necessary for regeneration driven by regeneration-associated gene expression. Here, we show that the lncRNA malat1, crucial for many biological functions, plays essential roles during retina regeneration. We demonstrate that malat1 functions through an Egr-dependent axis, modulated by Wnt, Notch, and TGF-{beta} signaling pathways, and is necessary for effective retina regeneration. Moreover, we uncover that the antisense lncRNA talam1, which regulates malat1 availability, is differentially regulated in zebrafish and mice, highlighting species-specific gene regulatory mechanisms after retinal injury. Cells with active TGF-{beta} signaling stabilize Malat1 in mice while the same signaling destabilizes malat1 in zebrafish. Taken together, our work uncovers a new role for the malat1/Egr1 axis in necessitating retina regeneration, which may have important implications for differential regenerative ability in vertebrates.

cell biology↗