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Professor Marianne Bronner, California Institute of Technology, Pasadena CA, USA

Title: Gene regulatory network underlying neural crest development

Venue: Lecture Theatre S3, Clayton Campus

Time: 4:00pm - 5:00pm

The neural crest is a population of multipotent, migratory progenitor cells that forms at the border of neural and non-neural ectoderm in vertebrate embryos. These cells then migrate from the neural tube along defined pathways, populate numerous sites and differentiate into diverse cells types including melanocytes, sensory and autonomic neurons, and mineralized matrices like bone and dentine. Data compiled from Xenopus, zebrafish, mouse and chick, suggest that a network of interacting transcriptional regulators and downstream effector genes confer properties like multipotency and migratory capacity to nascent neural crest cells.  These regulatory interactions can be divided into distinct phases.  The first involves inductive signals (e.g. Wnt, BMP, FGF) that establish the neural plate border, by up-regulation of border specifier genes like Msx1/2, Pax3/7, and Zic.  These border genes in turn up-regulate neural crest specifier genes like Slug/Snail, FoxD3 and the SoxE family.   Finally, the neural crest specifiers turn on specific downstream targets that render the neural crest migratory and multipotent. We are testing linkages in this hypothetical neural crest gene regulatory network by systematically perturbing a subset of the transcription factors involved in early neural crest 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 this putative neural crest regulatory network to identify neural crest enhancers, determine additional inputs to the network and determine which interactions are direct. The results suggest that a series of gene regulatory circuits are involved in the production of migratory neural crest cells in the early vertebrate embryos.  These are involved in inducing this population, maintaining its stem cell properties for a time and finally leading to progressive differentiation into derivatives as diverse as peripheral neurons, pigment cells and craniofacial cartilage.