Identification of a Novel Role of BMP Signaling in Enteric Neural Crest Colonization of the Zebrafish Enteric Nervous System
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 the processes that direct the migration, proliferation, and differentiation of the 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 situ transcript expression, immunohistochemical analysis, and chemical attenuation, I 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, I identified the expression of a novel ENS ligand-encoding transcript, bmp5, within the developmental regions of the ENCCs. Through the generation of a novel mutant bmp5wmr2, I identified a functional role for BMP5 in the proper colonization of the GI tract, whereby phox2bb+ 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 the proper formation of the vertebrate ENS.
Enteric Nervous System, Bone Morphogenetic Protein, Developmental Biology
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