# Development and Patterning of the Enteric Nervous System

> **NIH NIH R21** · STANFORD UNIVERSITY · 2023 · $431,336

## Abstract

Project Summary
 Failure in the onset of gastrointestinal (GI) motility, either in the context of prematurity or GI motility
disorders, is a significant cause of neurodevelopmental delay and mortality in the pediatric population. The
enteric nervous system (ENS), the local nervous system within the walls of the intestine, is the primary driver of
GI motility. We have recently demonstrated that enteric neurons are organized into a macrostructure of
circumferentially oriented stripes, which arise from progressive reorganization of enteric neurons from a random
array into neuronal stripes. The functional significance of this patterning is not understood, yet GI motility does
not arise until a timepoint when neuronal stripes have been established. Further, disruptions to ENS structure,
as occur in human diseases like Hirschsprung’s disease and in certain mouse models, are associated with GI
dysfunction. Here, we propose to characterize the development of this apparent structure-function relationship
in the embryonic and neonatal mouse ENS. We will further investigate the role of the patterning gene Taqpep in
ENS patterning and GI function. Taqpep has previously been shown to modulate striped cat coat patterning, and
our preliminary data suggest that Taqpep also influences the periodicity of enteric neuronal stripes. To establish
a relationship between structure and function during ENS development, we will map GI motility, neuronal
diversity, and neural network function onto the progressive striped patterning of the developing ENS (Aim 1). In
addition, we will investigate ENS patterning and GI motility in Taqpep mutant mice to determine how subtle
alterations to ENS patterning affect GI function (Aim 2). Overall, this project will characterize the relationship
between ENS structure and GI motility as well as uncover a molecular mechanism that controls ENS patterning
and GI motility. This novel understanding of ENS structure and function will yield critical basic insights into ENS
development and provide new avenues to interrogate the pathophysiology and treatment of GI immaturity and
pediatric GI motility disorders.

## Key facts

- **NIH application ID:** 10741619
- **Project number:** 1R21HD110950-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Julia Anna Kaltschmidt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $431,336
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10741619

## Citation

> US National Institutes of Health, RePORTER application 10741619, Development and Patterning of the Enteric Nervous System (1R21HD110950-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10741619. Licensed CC0.

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