Many birth defects result from failure of the establishment or maintenance of cell fate. Which gene products direct multi-potent embryonic precursor cells to adopt specific fates? How do they do so, and with what other genes or gene products do they interact? By answering these questions we hope to improve the ability of clinicians to diagnose and treat developmental disorders. In addition, the genes that regulate embryonic development are likely to be the ones that regulate the differentiation of adult stem cells. The basic biology of stem cells needs to be better understood before their therapeutic potential can be realized. Finally, virtually all genes important in cancer are also developmental genes. Thus, an improved understanding of gene regulatory networks that operated during embryonic development could benefit multiple clinical fields.
We focus on neural crest, a population of embryonic precursor cells with the potential to adopt diverse fates, including pigment cells, sensory neurons, muscle, cartilage, and autonomic neurons. The broad developmental potential of neural crest makes it a good model for the embryo in general, and a variety of debilitating diseases affect neural crest derivatives. We focus on gene pathways that regulate establishment and maintenance (survival) of specific neural crest lineages, and of neural crest per se.
In these studies we use zebrafish, a vertebrate model system well suited to genetic and embryological methods. We have projects focussed on, a) understanding why disruption of ion channel TRPM7 causes melanocyte death and embryonic paralysis, b) the role of transcription factor AP-2 proteins in neural crest specification and survival, and c) the role of transcription factor Irf6 in normal craniofacial development.