miR-203 regulates progenitor cell proliferation during adult zebrafish retina regeneration

Abstract

Damage of the zebrafish retina triggers a spontaneous regeneration response that is initiated by Müller Glia (MG) dedifferentiation and asymmetric cell division to produce multipotent progenitor cells. Subsequent expansion of the progenitor pool by proliferation is critical for retina regeneration. Pax6b expression in the progenitor cells is necessary for their proliferation, but exact regulation of its expression is unclear. Here, we show that miR-203 is downregulated during regeneration in proliferating progenitor cells. Elevated miR-203 levels inhibit progenitor cell expansion without affecting MG dedifferentiation or progenitor cell generation. Using GFP-reporter assays and gain and loss of function experiments in the retina, we show that miR-203 expression must be suppressed to allow pax6b expression and subsequent progenitor cell proliferation.

Retina regeneration in zebrafish

“…Indeed, a number of microRNAs have been identified that increase in response to retinal injury, some of which contribute to progenitor amplification 33 . However, microRNA suppression also plays an important role in retina regeneration with let7 and miR-203 suppression contributing to Müller glia reprogramming and progenitor proliferation, respectively 9,34 . miR-203 appears to inhibit proliferation of Müller glia-derived progenitors by suppressing Pax6b expression (Fig.…”

“…miR-203 appears to inhibit proliferation of Müller glia-derived progenitors by suppressing Pax6b expression (Fig. 2) 34 . A role for microRNAs in differentiation of progenitors in the injured retina remains unstudied, but is almost certain to have an important role.…”

Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell Populations that Contribute to Retina Growth and Regeneration

“…Although a number of secreted factors, genes and signaling molecules regulating MG proliferation have been studied (Conner et al, 2014; Fausett et al, 2008; Hochmann et al, 2012; Nelson et al, 2013; Nelson et al, 2012; Rajaram et al, 2014a; Rajaram et al, 2014b; Ramachandran et al, 2010a; Ramachandran et al, 2011, 2012; Raymond et al, 2006; Thummel et al, 2010; Wan, 2012; Wan et al, 2014; Yurco and Cameron, 2007; Zhao et al, 2014), the molecular logic connecting their activities to uninjured and injured retinal environments remains poorly understood. Here we provide evidence that Fgf8a helps link the retinal environment to signaling molecules and gene expression programs that regulate MG proliferation.…”

MiR-218 Induces Neuronal Differentiation of ASCs in a Temporally Sequential Manner with Fibroblast Growth Factor by Regulation of the Wnt Signaling Pathway

“…In this study, we analyzed miRNA expression profiling that significantly changed when ASCs were treated with RA for neuronal differentiation. We identified that certain miRNAs exhibited tremendous changes in their expression during differentiation (including let-7 family, miR-146a, miR-196b, miR-218, miR-214, miR-203, miR-124, miR-26a, miR-222, miR-375, miR-9 ), which have been shown to facilitate neurogenesis15313233343536.…”