Sarah Sarich, PhD Candidate in the Department of Biological Sciences at UWM, will present a talk entitled, “The Transcription Factor Jun is Necessary for Regulating Regeneration-Associated Gene Expression During Optic Nerve Regeneration.”

The abstract is as follows:

Damage to the axons of the central nervous system (CNS) in mammals results in permanent loss of function. For the axons that comprise the optic nerve, this loss of function is a consequence of the mature retinal ganglion cells’ (RGCs) failure to revert to a growth competent state. However, in adult zebrafish, regeneration-associated gene (RAG) expression facilitates the functional recovery of the RGCs within two weeks of optic nerve injury. In larval zebrafish, this timeline is significantly shorter, and RGC axons reach their targets within two to four days. This ability to initiate RAG expression in zebrafish suggests a regeneration program distinct from developmental gene expression. To implement this regeneration program, key regulators must orchestrate successive cascades of gene expression that instruct the RGCs to survive, regrow, navigate the visual path to the brain, and form synaptic connections. One such regulator that has been identified in peripheral nervous system (PNS) and CNS regeneration is the transcriptional activator, Jun. To investigate the role of Jun during optic nerve regeneration, we utilized transgenic fish that express green fluorescent protein (GFP) throughout the RGCs to visualize the optic nerve. A line of heat shock inducible Jun – dominant negative (Jun-DN) fish were created to knockdown Jun function and crossed into the GFP expressing line. We determined that jun is upregulated early in response to larval optic nerve transection, and its expression is sustained until synapses are reestablished. Previously identified putative Jun targets showed differing expression patterns in larval regeneration, and functional knockdown of Jun either upregulated or downregulated putative target expression. Furthermore, induction of Jun-DN caused fewer fish to show any signs of regeneration, leaving them with a nerve stump. These results validate jun as a key regulator for successful optic nerve regeneration, further distinguish the regeneration program from development, and advance our knowledge for the formation of future therapies to treat CNS damage.

The presentation will take place in Lapham Hall S160 at 4:00 PM, preceded by an informal reception from 3:45 – 4:00 PM.