Neural Crest Gene Regulatory Networks
The neural crest is an important stem cell population in the embryo characterized by its multipotency, migratory behavior, and broad ability to differentiate into derivatives as diverse as cardiomyocytes, craniofacial skeleton, and the peripheral nervous system. Underlying the development of these unique derivatives is a neural crest gene regulatory network (GRN) that describes the regulatory interactions at each stage of neural crest development. Our team is focused on understanding the regulatory networks controlling the development of the neural crest from a multipotent stem cell population into unique derivatives, how these networks are re-used during adult repair processes, how these networks become dysregulated at the onset of disease, and how these networks evolve to give rise to morphological novelties.
Neural Crest in Adult Regeneration
Our recent work reveals a previously unrecognized contribution of neural crest-derived cells to cardiomyocytes across vertebrates and their role during regeneration in the adult heart of zebrafish (Tang*, Martik*, et al, eLife, 2019). We are interested in how neural crest-derived cells and redeployment of an embryonic-like gene regulatory program control the de-differentiation and proliferation, fibrosis, and scar formation/regression during the cardiac regeneration process in zebrafish. Further, by uncovering GRN differences between amniote hearts, which lack the capacity to regenerate, and anamniotes with remarkable regenerative ability, our goal is to drive regeneration in systems where it otherwise fails to occur.
Neural Crest Evolution
Using the jawless fish, the sea lamprey, our lab group is working to understand the gene regulatory changes that drove the diversification of the neural crest and the evolution of vertebrates. Our previous work (Martik, et al, Nature 2019) found that the lamprey neural crest gene network is missing crucial information that is required for axial refinement of the neural crest. Throughout gnathstome evolution, the neural crest gene network was progressively elaborated to modulate differentiation capacity along the anterior-posterior axis. Our work aims to uncover the progressive assembly of a novel axial-specific regulatory circuits that allowed for the elaboration of the neural crest during vertebrate evolution.
Neuroblastomas emerge at sites along the sympathetic nervous system as a result of improper differentiation of neural crest-derived sympathoadrenal progenitors; however, the molecular mechanisms underlying the ontogeny of neuroblastoma are not fully understood. Determining the gene regulatory network circuitry underlying sympathoadrenal development and comparing this to that active at the onset of neuroblastoma holds the promise of yielding insights into new therapeutic genetic targets. Using the zebrafish as a model, our group is working to unravel the gene regulatory network controlling the differentiation of the sympathetic nervous system with the long term goal of providing information about potential therapies for prevention and treatment.