# Exploring neural crest stem cell-derived enteric neurogenesis in post-embryonic development and regeneration

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $175,392

## Abstract

PROJECT SUMMARY/ABSTRACT
 I am a gastroenterologist at UCLA, and I am committed to studying enteric neurogenesis to better
inform development of therapies for enteric neuropathies such as Hirschsprung disease, esophageal
achalasia, and gastroparesis. Historically, the enteric nervous system (ENS) was thought to be composed of a
finite pool of terminally differentiated neurons. This conception of the ENS supported therapeutic approaches
for enteric neuropathies that largely seek to ameliorate symptoms but do not correct the underlying
pathophysiology. Recently, this concept has been challenged by the identification of a novel source of enteric
neuronal progenitors that reside outside of the intestine, termed neural crest stem cells (NCSCs).
 This proposal outlines a 5-year research and career development plan that will prepare me to become
an independent physician-scientist engaged in high-level scientific research. My aims are to elucidate the
origin, migration dynamics, and molecular signaling of NCSC-mediated enteric neurogenesis in development
and regeneration. I will employ the zebrafish as my model organism as it overcomes several limitations faced
by other models and is amenable to innovative techniques. Aim 1 will survey the post-embryonic intestine for
resident ENS progenitors using in situ hybridization and single cell RNA sequencing. My preliminary work
supports the absence of ENS progenitors in the intestine. Aim 2 will employ an inducible Cre transgenic line
and time-lapse confocal microscopy to determine the origin and migration dynamics of NCSCs that give rise to
enteric neurons. This Aim will assess persistence of NCSC contributions to the ENS through development and
adulthood. My preliminary data provides evidence of NCSC-mediated enteric neurogenesis and supports the
basis of this Aim. Lastly, Aim 3 will explore the role of 5HT4 receptor agonists in the promotion of NCSC-
mediated enteric neurogenesis in development and regeneration. Zebrafish are amenable to two-photon laser
cell ablation, allowing ENS-specific injury by ablating individual enteric neurons. My preliminary work
demonstrates increased enteric neurogenesis with 5HT4 receptor agonists, supporting the pursuit of this Aim.
 Along with strong preliminary work and a well-conceived research plan, this proposal also includes an
outstanding and multidisciplinary team of mentors and advisors, a crucial aspect to a successful transition to
independence. My mentors, Dr. Bronner and Dr. Pothoulakis, are leaders in their respective fields of
developmental biology and cellular biology, and they are renowned mentors with a long history of successfully
training young investigators. I will also receive critical guidance from advisors with widely recognized expertise
in ENS development (Dr. Gershon), transcriptomics (Dr. Pachter), neurogenesis (Dr. Kornblum), and advanced
microscopy (Dr. Collazo). Together, with my extraordinary research environment, coursework and seminars,
and the...

## Key facts

- **NIH application ID:** 10127390
- **Project number:** 1K08DK123387-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Wael El-Nachef
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $175,392
- **Award type:** 1
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127390

## Citation

> US National Institutes of Health, RePORTER application 10127390, Exploring neural crest stem cell-derived enteric neurogenesis in post-embryonic development and regeneration (1K08DK123387-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10127390. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*