BMP signaling pathway member expression is enriched in enteric neural progenitors and required for zebrafish enteric nervous system development.

Background: The vertebrate enteric nervous system (ENS) consists of a series of interconnected ganglia within the gastrointestinal (GI) tract, formed during development following migration of enteric neural crest cells (ENCCs) into the primitive gut tube. Much work has been done to unravel the complex nature of extrinsic and intrinsic factors that regulate processes that direct migration, proliferation, and differentiation of ENCCs. However, ENS development is a complex process, and we still have much to learn regarding the signaling factors that regulate ENCC development.

Results: Here in zebrafish, through transcriptomic, in situ transcript expression, immunohistochemical analysis, and chemical attenuation, we identified a time-dependent role for bone morphogenetic protein (BMP) in the maintenance of Phox2bb⁺ enteric progenitor numbers and/or time of differentiation of the progenitor pool. In support of our in silico transcriptomic analysis, we identified expression of a novel ENS ligand-encoding transcript, bmp5, within developmental regions of ENCCs. Through generation of a novel mutant bmp5^wmr2 and bmp5 crispants, we identified a functional role for BMP5 in proper GI tract colonization, whereby phox2bb⁺ enteric progenitor numbers were reduced.

Conclusion: Altogether, this work identified time-dependent roles for BMP signaling and a novel extrinsic factor, BMP5, that is necessary for vertebrate ENS formation.