When I was a kid I was told that if you cut a worm into tiny pieces it would regrow into a bunch of new worms.  Well, I attempted this multiple times, but unfortunately my attention span was limited back then, and I never was disciplined enough to see the final outcome of this project.  Now as an adult (sort of) I am committed to the world of regeneration again, but this time I am interested in studying retinal regeneration in zebrafish.  Unlike the human retina, which receives all of its retinal neurons before birth, the zebrafish retina can continually add new retinal neurons throughout the life of the fish from two retinal progenitor populations.  Because these adult stem cell populations are active, they can also replace retinal neurons that have been lost due to damage.  I am interested in the molecular mechanisms behind this zebrafish retinal regeneration.  To stimulate this regenerative response, we introduce fish into constant intense light, which damages photoreceptors and subsequently signals Muller Glia to reenter the cell cycle.  They will provide new retinal progenitors that will migrate to the outer nuclear layer of the retina and eventually differentiate into rod and cone photoreceptors.  We performed a microarray analysis to find potential gene candidates that may be involved in one or all of these processes.  I am characterizing two of these potential gene candidates, stat3 and olig2.  Stat3 is a cell signaling protein which also functions as a transcription factor.  Olig2 is a bHLH transcription factor that that plays a role in neuronal cell differentiation. I utilize polyclonal antiserum specific to these proteins, which I created, transgenic zebrafish lines, and molecular techniques to study their expression.  I also use morpholino-mediated knockdown of these proteins during regeneration to learn more about their function during this process. 

So, I guess you could say, my attention span for regeneration research has improved a bit since I was a kid, and I’m only left to wonder, what ever happened to those little worm pieces?

Figure 1.  At 16 hrs of light exposure, EGFP-expressing Müller cells (green signal, Panel A) also express Stat3 protein (red signal, Panel B) within their nuclei in the INL (merged image, Panel C).  At 16 hrs of light exposure, Stat3-expressing cells (green signal, Panel D and Panel F) co-localized with HuC/D-positive cells in the GCL ( Panel F), but not with the HuC/D-positive amacrine cells in the INL (red signal, Panels E and F) as shown in the merged image (Panel F).

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