Our group is interested in the gene regulatory networks (GRNs) that govern the decision of multipotent embryonic precursor cells to differentiate into one or another adult cell type. We study this question in the context of early blastomeres and the neural crest. We are also interested in the GRN that governs the decision of melanocyte stem cells to remain quiescent or to divide and differentiate.
We use zebrafish to explore these questions. We are examining the regulatory hierarchy of transcription factors in the GRN that promotes embryonic precursor cells to become periderm, a tissue that is essential for normal morphogenesis of the face and whose disruption leads to orofacial cleft. In addition, we are exploring how the transcription factors TFAP2 and MITF regulate melanocyte stem cell deployment. Working with colleagues in human genetics, we also have a project to distinguish the functional subset of DNA variants, both coding and non-coding, that are associated with risk orofacial cleft.
Maintenance versus deployment of stem cells is a fine balance: too far in one direction and there can be problems with wound healing and tissue maintenance, too far in the other can lead to cancer. Understanding the GRNs that govern this balance will lead to the development of therapies that can tip the balance one way or the other in patients as needed.