Advancements in our Understanding of Enteric Formation and Function

Abstract

Establishing the Enteric nervous system (ENS) relies heavily upon migration, colonization, and proper neural diversification to ensure a functional digestive tract. This dissertation investigates the role of Sox10 in ENS development and its potential implications for ENS function. Single-cell RNA sequencing during early ENS development reveals distinct neuronal trajectories and upregulation of Hox gene regulatory network activity as cells transition toward neuronal states. Differential expression analysis identifies significant downregulation of Hoxa6 within Branch C, indicating the involvement of Hox genes in neuronal diversification. Comparisons between Sox10+/+ and Sox10Dom/+ lineages highlight differences in the cellular landscape, underscoring Sox10's regulatory role in ENS development. Additionally, introducing the Sox10 MS mouse model aims to enhance cost-effectiveness and efficiency in Sox10-related studies. This model detects spontaneous calcium activity at the wavefront of migrating enteric progenitors and increased calcium activity in the enteric glia of Sox10Dom/+ offspring, suggesting Sox10's involvement in calcium signaling within the mature ENS. The data presented in this thesis serve as a foundation for further exploration of ENS development at the transcriptomic level and expand the available tools for research in enteric studies.