Dr. Cornell's laboratory uses zebrafish to dissect the genetic pathways that govern lineage choice and differentiation in the embryonic ectoderm. One long-standing focus is the role that members of the transcription factor AP-2 family (e.g. Tfap2 alpha, Tfap2 gamma, Tfap2 epsilon) play in inducing the neural crest, and in the resulting specification and differentiation of melanocytes from the neural crest. Another project addresses the role of transcription factor IRF6 in the development of early-forming epithelial layers, including the enveloping layer (EVL), which surrounds zebrafish embryos starting at the early blastula stage. Notably, in humans, defects in trophectoderm (TE) development can cause spontaneous abortion at the implantation stage, and in collaboration with Dr. Brian Schutte in the Department of Pediatrics, Dr. Cornell's laboratory has generated evidence suggesting that the EVL-governing pathway in which IRF6 participates plays a conserved role in TE development. An additional project aims to understand why a zebrafish transient receptor potential melastatin 7 (TRPM7) mutant lacks melanocytes and is paralyzed at embryonic stages. The molecular phenotype in this model appears to be relevant to Parkinson?s disease and is a new area they are investigating of relevance to the Center. Finally, research in the zebrafish model is impeded by the absence of a gene knockout technology; an additional focus of the laboratory is to develop adeno-associated virus as a vector for gene targeting in zebrafish, which would facilitate forward genetics in this species and its use in disease modeling. This work is being conducted in collaboration with Dr. Ziying Yan, an expert in AAV, and Dr. Paul Collodi, an expert in zebrafish stem cells (Purdue University). The Cornell group has generated a transgenic zebrafish harboring a mutant-GFP reporter gene (which lacks fluorescence due to a single base pair change) to use in the development of gene targeting strategies with AAV or any other vector.
Selected Publications:
Elizondo, M. R., Arduini, B. L., Paulsen, J., Sabel, J. L., MacDonald, E. L., Henion*, P. D., Cornell* R. A., Parichy*, D. M. (2005) Defective skeletogenesis and kidney stone formation in dwarf zebrafish mutant for trpm7, Current Biology, 15: 667-671. *Co-corresponding authors
Nair, S., Li, W., Cornell, R. A. and Schilling, T. F. (2007) Endothelin-1 dependent signals from facial ectoderm regulate jaw and pharyngeal arch patterning in the zebrafish embryo. Development, 134(2):335-45.
Li, W. and Cornell, R. A. (2007) Tfap2a and Tfap2c act redundantly to specify neural crest and promote early development of placode derivatives in zebrafish. Developmental Biology, 304(1):338-54
McNeill, M.S., Paulsen, J., Bonde, G., Burnight, E., Hsu, M.Y., and Cornell, R.A. (2007). Cell death of melanophores in zebrafish trpm7 mutant embryos depends on melanin synthesis. J Invest Dermatol 127:2020-2030.
