Defining the transcriptomic landscape of the developing enteric nervous system and its cellular environment

摘要: Motility and the coordination of moving food through gastrointestinal tract rely on a complex network neurons known as enteric nervous system (ENS). Despite its critical function, many molecular mechanisms that direct development ENS elaboration neural connections remain unknown. The goal this study was to transcriptionally identify pathways candidate genes drive specification, differentiation circuitry specific progenitors, phox2b expressing cell lineage, during normal development. Because is tightly linked environment, transcriptional landscape cellular environment intestine also analyzed. Thousands zebrafish intestines were manually dissected from transgenic line green fluorescent protein under regulatory elements [Tg(phox2b:EGFP) w37 ]. Fluorescence-activated sorting used separate GFP-positive progenitor derivatives GFP-negative intestinal cells. RNA-seq performed obtain accurate, reproducible profiles unbiased detection low level transcripts. Analysis revealed may function in determination, be identifiers different subtypes, define non-neural microenvironment ENS. Differential expression analysis between two populations expected neuronal nature lineage including enrichment for required neurogenesis synaptogenesis, identified novel not previously associated with Pathway pointed high G-protein coupled pathway activation, roles such Nogo/Reticulon axon guidance We report comprehensive gene lineage-specific population their derivatives, Our results confirm implicated development, scores pathways. Thus, our dataset suggests various potential facilitating characterization discovery therapeutic strategies improve disorders.