# Genetic and epigenetic regulation of cranial neural crest differentiation

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $430,003

## Abstract

How cells become specified and differentiate at the correct time and place is a fundamental question in
developmental biology. Cranial neural crest cells (cNCCs) are an excellent model system to understand this
process due to the multipotent nature of the progenitor cells, generally unrestricted developmental potential
with known lineage and derivatives, and defined gene regulatory networks. In addition to the gene networks,
epigenetic regulators can affect the expression of numerous target genes and may help to explain the
differences in penetrance and phenotype between individuals with the same genotype. This is important since
defects in neural crest development underlie many human congenital birth defects, such as cleft lip with or
without palate and many craniofacial syndromes. Thus, understanding the genetic and epigenetic regulators in
cNCC development is key to understanding how cell fate is determined. We hypothesize that PRDM
paralogs regulate global gene expression by regulating downstream targets oppositely, including Wnt
pathway components, to control the timing of cartilage/bone differentiation within the cNCC lineage.
The rationale for the proposed studies is that an in depth understanding of normal cNCC development will
provide insights into normal biology and the etiology of neural crest-associated birth defects, many of which are
thought to arise from cNCC abnormalities. We will test this hypothesis in the following specific aims: 1) Test
the hypothesis that PRDM proteins act upstream of Wnt signaling to control the timing of cNCC
differentiation into chondrocytes. We will test the hypothesis PROM paralog activity is required in cNCCs
cell autonomously upstream of Wnt signaling to promote differentiation of chondrocytes. 2) Test the
hypothesis that Prdm3 and Prdm16 genetically interact to regulate cNCC gene expression and
chromatin accessibility. In Aim 2, hypothesis that Prdm3 and Prdm16 genetically interact to control gene
expression via regulating transcription and chromatin modification specifically at cNCC and Wnt gene targets.
3) Test the hypothesis that Prdm3 regulates global gene expression by controlling the timing of
genomic accessibility of Prdm16. In Aim 3, we will test the hypothesis that loss of Prdm3 leads to global
alterations in chromatin state at cNCC progenitor genes via changes in binding of Prdm16 throughout the
genome, which controls the liming of cNCC differentiation into chondrocytes. Together, these studies will
reveal basic information of how cNCCs differentiate into specific cell types during development. The results of
this proposal have the potential to reveal important new insights into cNCC development and how these
processes go wrong in disease, with the hope of providing a foundation for the design of therapeutic strategies
for neural crest associated birth defects.

## Key facts

- **NIH application ID:** 10316019
- **Project number:** 1R01DE030377-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kristin Artinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,003
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316019

## Citation

> US National Institutes of Health, RePORTER application 10316019, Genetic and epigenetic regulation of cranial neural crest differentiation (1R01DE030377-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10316019. Licensed CC0.

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