# Lineage and transcriptional analysis of sacral neural crest contribution to the enteric nervous system

> **NIH NIH F31** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2023 · $47,694

## Abstract

Proposal Summary
 The enteric nervous system (ENS) is a vital part of the peripheral nervous system and is responsible for
the control of critical gut functions like peristalsis and gastrointestinal secretion. Abnormal development of the
ENS can lead to life threatening disorders like Hirschsprung’s disease, characterized by the absence of
innervating neurons and glia in the gut. Seminal experiments in chick have shown that two distinct neural crest
cell populations innervate the gut and give rise to the ENS: the vagal and the sacral neural crest. Although
extensive research has been done on the vagal neural crest’s contribution to the ENS, very little is known about
the role of the sacral neural crest in the post-umbilical gut. We aim to address this gap in knowledge by using
modern-day molecular biology techniques to gain granular understanding of sacral neural crest-
derivatives in the post-umbilical gut, characterize their unique gene signatures, and determine the
requirement of sacral-specific transcriptional regulators in ENS development. We hypothesize that the
sacral neural crest contributes to unique derivatives within the post-umbilical gut, distinct from vagal-derived
structures, and that these derived-cells are under the regulation of a novel gene regulatory scheme. Ultimately,
this work will address a lack of understanding of the sacral neural crest in ENS development and shed light on
the etiology of ENS-derived congenital disorders.
Aim 1: Retroviral mediated lineage analysis of the chick sacral neural crest: Previous work in quail-chick
chimeras had multiple disadvantages like traumatic surgery and cross-species artifacts. Here we will implement
our technique of replication incompetent avian (RIA) retroviruses for comparative cell lineage analysis of vagal
and sacral-derived cells in the post-umbilical gut, visualize interactions between the two populations, and perform
clonal analysis of sacral neural crest cells.
Aim 2: Transcriptional profiling of sacral neural crest-derived cells in the post-umbilical gut: In order to
identify the gene signature of sacral-derived structures of the ENS and regulators of their differentiation, we
propose single cell RNA sequencing of sacral neural crest derivatives across multiple time points to characterize
the transcriptional profile of sacral neural crest entry into the gut and neuronal differentiation. Upon identification
of transcriptional regulators, we will perform conditional loss-of-function analysis to examine their role in
regulating the sacral neural crest’s neuronal differentiation.

## Key facts

- **NIH application ID:** 10679674
- **Project number:** 1F31HD111287-01A1
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** JESSICA JACOBS-LI
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679674

## Citation

> US National Institutes of Health, RePORTER application 10679674, Lineage and transcriptional analysis of sacral neural crest contribution to the enteric nervous system (1F31HD111287-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10679674. Licensed CC0.

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