# Defining the functional role of Bone Morphogenic Protein Signaling Pathway in the formation of the enteric nervous system

> **NIH NIH F31** · RICE UNIVERSITY · 2020 · $45,520

## Abstract

The enteric nervous system (ENS) is the intrinsic nervous system within the muscle walls of the
entire gastrointestinal (GI) tract. The ENS consists of a series of interconnected enteric ganglia
and is responsible for mediating peristalsis, water balance, and regulation of local GI hormonal
secretions. While much recent progress has been made in understanding how the ENS
functions, far less is known about its formation during early embryological development. During
development, neural crest cells (NCCs) that contribute to the ENS immigrate into the primitive
foregut and navigate caudally along the gut length to its distal end, during which time they are
referred to as enteric neural crest cells (ENCCs). A failure of ENCCs to fully populate the gut
and differentiate into neurons leads to improper ENS development and results in the congenital
disease, Hirschsprung Disease, which is characterized by a lack of enteric ganglia along
variable regions of the GI. While ENCCs migrate along the primitive gut, they receive various
extrinsic signals—such as GDNF, Retinoic Acid and Sonic Hedgehog—from the surrounding gut
tissues and neighboring ENCCs that promotes their proliferation, migration, differentiation and
multipotency. Indeed, while the field has characterized some of the signaling pathways that are
important for colonization of the gut by the ENCCs, the gene regulatory and molecular
mechanisms that link extrinsic signals to ENCC migration and neuronal specification is poorly
elucidated.
My strong in vivo imaging-based and transcriptomic preliminary data using zebrafish embryos
indicates that the Bone Morphogenetic Protein (BMP) signaling pathway is highly enriched in
migrating ENCCs and is required in a temporally-specific manner for their colonization and
neuronal differentiation along the gut. Zebrafish embryos afford the unique opportunity to readily
study development of the ENS due to their transparent, external, and rapid development. This
proposal tests the hypothesis that BMP signaling directly regulates colonization of the gut by
ENCCs and their timely differentiation to dictate the establishment of ENS. The specific aims of
this proposal are 1. To map the spatiotemporal expression of BMP pathway members and BMP
pathway activity in the developing zebrafish ENS, 2. Uncover the cellular mechanisms by which
BMP signaling controls ENCC gut colonization. The results of these experiments will elucidate
the molecular mechanism driving ENS development and expand the gene regulatory network
that modulates the colonization of the GI tract by neural crest cells.

## Key facts

- **NIH application ID:** 10154909
- **Project number:** 1F31HD104474-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Joshua A Moore
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-09-25 → 2024-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154909

## Citation

> US National Institutes of Health, RePORTER application 10154909, Defining the functional role of Bone Morphogenic Protein Signaling Pathway in the formation of the enteric nervous system (1F31HD104474-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10154909. Licensed CC0.

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