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

Abstract

The vertebrate enteric nervous system (ENS) consists of a series of interconnected ganglia within the gastrointestinal (GI) tract, formed during development following the 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 the 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. Here in zebrafish, through transcriptomic,in situtranscript 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 ourin silicotranscriptomic analysis, we identified expression of a novel ENS ligand-encoding transcript,bmp5,within developmental regions of ENCCs. Through generation of a novel mutantbmp5wmr2,we identified a functional role for BMP5 in proper GI tract colonization, wherebyphox2bb+enteric progenitor numbers were reduced. Altogether, this work has identified time-dependent roles for BMP signaling and identification of a novel extrinsic factor, BMP5, that is necessary for proper formation of vertebrate ENS.

Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo

“…We then asked if chemical inhibition of the BMP pathway could recapitulate the effect MYCN overexpression had regarding the aberrant expression of NCC genes in developing SCG of zebrafish larvae. For this, we used K02288, a BMP inhibitor previously validated (57,58), to attenuate BMP signaling at 48 hpf, a time during the onset of sympathetic differentiation (59).…”