Mesendodermal neural crest interactions during enteric nervous system precursor migration

The enteric nervous system (ENS) is the largest most complicated subdivison of the peripheral nervous system and is completely derived from the neural crest. ENS precursor fate specification is determined by regulative interactions within the premigratory crest and subsequent interactions between the migrating ENS precursors themselves and their surrounding tissues. These interactions determine the migratory pathway the precursor cells follow to the intestine, the number of enteric neurons and glia that the precursors will generate, and the final ENS neuron specific phenotype they will acquire. In zebrafish, the entire ENS is derived from only post‐otic neural crest cells. To identify molecular regulators of enteric precursor migration and ENS cell fate determination we have taken a classical forward genetic approach. We screened for zebrafish mutants that display aberrant neural crest/ ENS phenotypes. To date we have identified 6 novel ENS mutants and the genetic basis of 3 of these mutants has been determined. A striking feature of all of these mutants is that in addition to their ENS phenotypes all of the mutants display varying degrees of abnormal endodermal development. This has led to our hypothesis that the endoderm is a critical signaling center required for normal ENS precursor migration and ENS development. I will discus our latest findings supporting this hypothesis. This work is supported by grant funding from NIDDK.