Department of Anatomy, Physiology, and Cell Biology
University of California, Davis
Title: Identifying conserved and divergent regulators of neural crest formation and EMT
Abstract: The formation and physical separation of the three ectodermally-derived cell types—the non-neural ectoderm (epidermis and placodes), the neural ectoderm (central nervous system, CNS), and the neural crest (NC)—occurs almost simultaneously during vertebrate development. This process coincides with dynamic changes in transcription factors that alter the expression of cell-cell adhesion molecules, which allow for the NC epithelial to mesenchymal transition (EMT). However, transcriptional control of cell adhesion is a slow process, and therefore cells must employ faster methods like intracellular trafficking to transport epithelial and migratory cell adhesion molecules (cadherins) to and from the membrane during EMT. Type I epithelial cadherins and type II migratory cadherins are expressed in distinct and overlapping patterns as NC cells undergo EMT. Specifically, neural cadherin (CDH2) is expressed in the CNS, but is absent from premigratory cranial NC cells, while epithelial cadherin (CDH1) and cadherin-11 (CDH11) are co-expressed as collective migration commences. We have identified that transcription factors work together with β-III tubulin (TUBB3)-dependent microtubule-mediated trafficking mechanisms to regulate rapid changes in cadherin protein expression and localization to regulate development. We have identified an in vivo multi-mechanistic framework that regulates cell adhesion during NC cell EMT and CNS differentiation.