Gene regulatory interactions mediating formation of neural crest and placodes

Abstract

During development of vertebrate embryos, the peripheral nervous system of the face arises from two cell types: neural crest cells and cranial ectodermal placodes. Cranial placodes arise from regions of thickened ectoderm in the embryonic head that invaginate and/or delaminate to give rise to portions of the cranial ganglia as well as sensory structures like the ear, lens, and nose. While peripheral ganglia of the trunk are exclusively neural crest-derived, those arising at cranial levels have a dual origin from both neural crest and placodes. Like neural crest cells, placodal cells migrate and undergo epithelial to mesenchymal transitions. In addition, their progeny are similar: both can form sensory neurons, neuroendocrine cells, and cells that can secrete special extracellular matrices. We hypothesize that distinct gene regulatory networks lead to formation of neural crest cells and placodes. We are testing linkages in these hypothetical gene regulatory networks by systematically perturbing a subset of the transcription factors involved in early specification and examining the effect of these perturbations on likely downstream genes in order to test the predicted interrelationships. In addition, we are isolating cis-regulatory regions of genes in thes putative neural crest regulatory network to identify enhancers, determine additional inputs to the network and determine which interactions are direct.