Abstract: Regeneration has largely been studied using paradigms requiring multiple tissues or cell types to be replaced. In these contexts, the regenerative process is often said to “recapitulate development”, exhibiting many parallels with tissue histogenesis. In contrast, paradigms involving the selective ablation of discrete cell types can elicit “fate-biased” regenerative processes, where progenitor cells preferentially give rise to the lost cell type. How “fate-biased” regeneration is regulated is unknown. To begin to address this question, we are performing a CRISPR/Cas9-enabled reverse genetic screen to identify factors that promote or inhibit retinal ganglion cell (RGC) regeneration following selective RGC ablation in zebrafish. Interestingly, disruption of the basic helix-loop-helix transcription factor ascl1a – a gene previously suggested to be required for retinal regeneration following widespread cell loss or traumatic injury – resulted in accelerated RGC replacement kinetics. This is in keeping with Ascl1 acting to inhibit RGC fate during retinal development in mice and suggests that loss of ascl1a, in the context of selective RGC ablation, serves to bias retinal progenitors toward RGC production during regeneration. In an effort to identify transcription factors associated with RGC fate bias, we are using a single-cell multiomics approach to compare retinal progenitor cell profiles in control and ascl1a-disrupted retinas following selective RGC ablation. Preliminary results from these studies will be discussed.
This seminar is hosted by Dr. Romain Madelaine
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https://mdibl-org.zoom.us/j/94400602229?pwd=K2lTRmZmTUFTaGtQZHprZDcxbU02UT09
Meeting ID: 944 0060 2229
Passcode: Seminars