Functional dissection of the master regulator of zebrafish endoderm cell fate specification Sox32/Casanova

Endoderm, one of the three primary germ layers of the vertebrate embryo makes major contributions to the respiratory and gastrointestinal tracts and all associated organs including the liver and pancreas. Expression of the transcription factor Sox32 (otherwise known as Casanova) is the last step in a complex molecular cascade leading to endoderm fate in zebrafish. Sox32 is considered to be the master regulator of endoderm specification since mutant embryos completely lack endoderm, while overexpression produces ectopic endoderm. The importance of Sox32 is therefore clear, and its regulatory inputs have been broadly studied. How Sox32 functions at the molecular level, however, is less well understood, and its known physical and genetic interactions are insufficient to explain its regulation of endoderm fate. This project aims to reveal the chromatin-level regulatory mechanisms underlying Sox32-mediated induction of endoderm fate. It will be achieved through a combination of functional genomics, high-throughput proteomics, genome editing, bioinformatics and embryology. It will provide key insights into gene regulatory control of a critical cell fate decision during early embryogenesis, and potentially inform future cellular reprogramming approaches.