Serjanov, D. | bioRxiv Science

bioRxiv2025

Regulation of Adult Zebrafish Retinal Regeneration by Lamβ1b-Chain-Containing Laminins

Retinal degenerative diseases are a major cause of blindness in humans that often result in permanent and progressive loss of vision. Unlike humans, zebrafish possess the remarkable ability to regenerate lost retinal neurons through Muller glia (MG) reprogramming and asymmetric cell division to produce multipotent retinal progenitor cells (RPCs). While most studies on the molecular mechanisms underlying this regeneration process have focused on intracellular mechanisms, the role of the microenvironment surrounding retinal cells, the extracellular matrix (ECM), has been understudied. Laminins are heterotrimeric glycoproteins, are principal components of the ECM basement membrane, and play important roles in vertebrate retinal development. Here, we examine the role of {beta}1b chain-containing laminins in the regenerative response of the zebrafish retina. We found that the zebrafish lamb1b gene is differentially expressed during MG reprogramming and MG and NPC proliferation during retinal regeneration. Further, we found that {beta}1b-containing laminins play important roles in regulating MG and NPC proliferation and neuroprotection of photoreceptors in light-damaged zebrafish retinas. Finally, Lam{beta}1b plays an important role in regulating the expression of integrin receptors and other laminin genes during the regeneration response. Taken together, Lam{beta}1b, and likely other ECM components, play a critical role in the MG-dependent neuronal regeneration response in the zebrafish retina.

neuroscience↗

bioRxiv2023

Common and divergent gene regulatory networks control injury-induced and developmental neurogenesis in zebrafish retina.

Following acute retinal damage, zebrafish possess the ability to regenerate all neuronal subtypes. This regeneration requires Muller glia (MG) to reprogram and divide asymmetrically to produce a multipotent Muller glia-derived neuronal progenitor cell (MGPC). This raises three key questions. First, does loss of different retinal cell subtypes induce unique MG regeneration responses? Second, do MG reprogram to a developmental retinal progenitor cell state? And finally, to what extent does regeneration recapitulate retinal development? We examined these questions by performing single-nuclear and single-cell RNA-Seq and ATAC-Seq in both developing and regenerating retinas. While MG reprogram to a state similar to late-stage retinal progenitors in developing retinas, there are transcriptional differences between reprogrammed MG/MGPCs and late progenitors, as well as reprogrammed MG in outer and inner retinal damage models. Validation of candidate genes confirmed that loss of different subtypes induces differences in transcription factor gene expression and regeneration outcomes. This work identifies major differences between gene regulatory networks activated following the selective loss of different subtypes of retina neurons, as well as between retinal regeneration and development.

neuroscience↗