David M. Hollis, PhD, Furman University
PROJECT TITLE: Transcriptomic analysis of the adult teleost fish brain early response to injury
A tremendous discrepancy occurs between the different vertebrate classes with regard to their capacity for adult brain repair. Of the different vertebrates, adult teleost fish exhibit the greatest neural regenerative capability as they readily replace damaged neurons with a concomitant lack of inflammation, cavitation, and scarring. Understanding the molecular mechanisms that allow fish this capacity has the potential to elucidate the causal limitations of the other vertebrates, including mammals. In this project, it was proposed to:
- establish a teleost fish, the mummichog (Fundulus heteroclitus) as a model for examining the molecular mechanisms of neuronal repair in a brain-regenerative-capable adult vertebrate and
- utilize a simple surgical technique to administer mechanical lesions to the brain of the adult mummichog to instigate the brain repair and regenerative process and
- collaborate with the Medical University of South Carolina Proteogenomics Facility to perform RNA-sequencing to characterize the early brain response (1hr) post-injury.
The data from this work was intended to provide insight into the pathways that govern the cellular processes known to occur in the fish brain in the acute response to injury and as to whether the paths involved in adult brain repair are intrinsic and recapitulate paths in neural development or are distinct from developmental processes.
This project simply would not have occurred without SC INBRE Bioinformatics Pilot Project Program funding. The grant allowed for the use of RNAseq2, as well as the analysis of the data acquired from RNAseq2. Both of these factors made up the bulk of the costs of the project. It should also be noted that the completion of this project has allowed our lab the potential to identify functionally relevant genes by means of objective data, allowing us to avoid the pitfalls of the candidate gene approach.
The data from this work provides insight into the pathways that govern the cellular processes known to occur in the fish brain in response to injury that allow for successful brain repair. Further, the project may provide insight into the causal limitations of the severely limited mammalian brain regenerative capacity as well. Regardless, it will begin to offer valuable information into whether the paths involved in adult brain repair are intrinsic and recapitulate stages of neural development or whether distinction from developmental processes exists in the adult brain regenerative process.
February 2, 2018