Neural crest cells migrating in vitro.

Putative Gene Regulatory Network for Vertebrate Neural crest.

Transverse section through the invaginating otic placode in chicken. Magenta marks E-cadherin protein and blue marks nuclei.

Neural Crest Cell Emigration and Migration

Neural crest cells are among the most migratory cell type in vertebrate embryos.  We are characterizing the machinery responsible for neural crest cell movement, the nature of the neural crest epithelial to mesenchymal transition to form a migratory cell type and the role of the migratory environment in influencing migratory pathway choices.  A variety of cell labeling techniques, including DiI-labeling, microsurgical grafts and confocal time-lapse microscopy, are used to follow the pathways of neural crest migration in a variety of vertebrates, including chicken, zebrafish and lamprey.  We are utilizing loss-of-function analysis, ectopic expression and transcriptomics to unravel the genes involved intrinsically in neural crest migration and the role of the microenvironment in influencing pathway choice.

Induction and Gene Regulation of the Neural Crest

We study the signaling and transcriptional interactions that lead to neural crest formation both at the tissue and the molecular level.  Currently, we are applying gain- and loss-of-function approaches coupled with transcriptome, regulatory analysis and bioinformatics to interrogate the molecular interactions that comprise a neural crest gene regulatory network (NC-GRN).  We are also examining the role of epigenetic modifications in early in neural crest development and how they influence the NC-GRN.

Early Patterning and morphogenesis of the Placodes

Ectodermal placodes give rise to cranial ganglia and sense organs (ear, nose, lens).  We are studying the molecular basis underlying formation and specification of the ectodermal placodes in fish and chicken embryos, with emphasis on induction, lineage decisions and morphogenesis.  The goal is to formulate the gene regulatory network responsible for formation of specific placodes.  Currently, we are focusing on specification and morphogenesis of the otic placode.

Lamprey is the most basal vertebrate.

Evolution of the Neural Crest and Placodes

The neural crest is a uniquely vertebrate innovation  We are cloning orthologues of neural crest and placode “marker genes” from a basal vertebrate (lamprey) and non-vertebrate chordate (amphioxus) as well as isolating regulatory regions for these markers. We are using loss-of-function approaches, transcriptome analysis and interspecific transplantation to dissect the basal NC-GRN and what may have driven evolution of jawed vertebrates. 

Melanoma cells in culture.

Neural Crest and Cancer

Neural crest cells are a highly multipotent cell type that gives rise to diverse derivatives including melanocytes, craniofacial skeleton and peripheral ganglia.  Many of the cell types are prone to metastasis in the adult, forming melanomas, neuroblastomas, and other types of metastatic cancer.  We are interested in comparing the mechanisms of neural crest invasive behavior with those causing adult neural crest derivatives to return to a migratory and invasive state.