Elucidating the molecular basis of neural crest cell EMT, migration, and intercellular interactions
The Taneyhill lab studies the vertebrate neural crest, a transient population of migratory cells that ultimately differentiate to become a wide range of structures, including the peripheral nervous system, pigment cells (melanocytes), and the bones and cartilage of the face and neck. Consequently, many human congenital and hereditary malformations (craniofacial abnormalities, heart defects), diseases (Hirschprung) and cancers result from aberrant neural crest development. Neural crest cells detach from the neural tube and migrate away into the periphery by undergoing an epithelial-to-mesenchymal transition (EMT) characterized by the loss of various epithelial properties (for example, cell-cell adhesion) and the subsequent acquisition of a mesenchymal (motile) phenotype, an event molecularly similar to EMTs observed in metastatic or invasive cancers when cells leave the primary tumor site.
Our lab is studying neural crest formation in the avian (chicken) embryo to better understand overall animal growth and development. The chicken provides an excellent model system for understanding neural crest development for a number of reasons: 1) The embryo is large and develops externally, making it amenable to both in ovo (in the egg) and in vitro manipulations; 2) the availability of the genomic sequence allows us to do molecular biology and biochemistry-based assays; and 3) the wealth of descriptive literature detailing neural crest development gives a rich history upon which we can draw for our studies. Thus, the chicken is the ideal organism in which to study the neural crest and elucidate how abnormalities in neural crest development give rise to various diseases, disorders and cancers. To address these effects on health and proper development, we must first ask some general questions about neural crest formation. How do these cells arise in the dorsal neural tube, and what distinguishes them from the rest of the neural tube? What molecular cues transform these non-motile precursors (the premigratory neural crest) to migratory neural crest cells? The Taneyhill Lab has now shown that components of cellular junctions play critical roles during neural crest cell EMT and later on when migratory neural crest cells intermingle and coalesce with placode cells to form the cranial ganglia. Collectively, we aim to establish a molecular blueprint for EMT and intercellular interactions in order to properly build and pattern the vertebrate embryo. Our results will have direct implications to overall animal and human health and development.