Decoding the early specification program of neural crest cells

The study of gene-regulatory networks is the key to understanding how a combination of transcription factors may orchestrate the development of an individual cell, ultimately leading to its differentiation.

Neural crest(NC) is an excellent developmental model for studying how cell fate decisions are made in the embryo, starting from multipotent progenitors.

Defects in NC formation are involved in roughly 1/3 of births with developmental anomalies and understanding the sequence of cell fate decisions will help us treat, rectify and attenuate adverse outcomes in the future.

In this project, I aim to decode a network of transcription factors and chromatin-associated activities that control specific cell fate decisions in the neural crest cells using high-throughput new technologies. As one of the first zygotically expressed genes, FoxD3 controls neural crest specification.

It acts in a bimodal fashion, to first prime neural crest program by affecting chromatin status, and later as a transcriptional switch to promote specific derivative fates.

Here I propose to investigate FoxD3 interactome to tackle mechanistic detail of how collaboration with context-specific interaction protein partners may lead to FoxD3 dual role, first defining neural crest multipotency and subsequently restricting it to specific cell lineage decisions.

This work will help the understanding of the fundamental mechanisms of NC specification, allowing us to tackle mechanisms of developmental neurocristopathies