# Post-transcriptional regulation of signaling systems during neural crest induction

> **NIH NIH F31** · CORNELL UNIVERSITY · 2022 · $20,370

## Abstract

PROJECT SUMMARY/ABSTRACT
The neural crest is a multipotent embryonic stem cell population that gives rise to most of the craniofacial
skeleton including cartilage and bone. Misregulation of neural crest development results in several craniofacial
anomalies and birth defects. Thus, elaboration of the processes guiding neural crest formation is imperative for
diagnosis and treatment of pathologies associated with this cell type. Neural crest cells are induced by the
combined action of signaling systems at the neural plate border, a stripe of progenitor cells adjacent to the
neural plate. Opposing morphogen gradients of Wnts and FGFs are central for progenitor cells to decide
between these two fates: induction of the neural crest requires high levels of Wnts and low levels of FGFs,
while high levels of FGFs drive cells towards a neural fate. Recent studies highlight the requirement of a
precise combination of signals for neural plate border induction, but we still have a superficial understanding
for how levels of FGF and Wnt are fine-tuned to jumpstart the neural crest genetic program. A regulatory
mechanism that may play a central role in tittering the activity of signaling pathways during early embryonic
development is microRNA (miRNA) mediated gene silencing.4 Intriguingly, we found that inactivation of the
miRNA pathway via knockdown of Dicer in avian embryos results in expansion of the neural plate territory at
the expense of neural crest cells. Furthermore, we have recently employed small RNA-sequencing to identify
miRNAs enriched in the neural crest. Our preliminary analysis of this dataset has indicated that neural crest
miRNAs (i) are regulated by canonical Wnt signaling and that (ii) they target important components of the FGF
signaling pathway. Accordingly, we hypothesize that Wnt signaling activates the expression of a set of miRNAs
that inhibit FGF signaling to promote neural crest formation. To test our model, we will use genomic, functional,
and biochemical approaches to define the regulation and function of Wnt-activated miRNAs in the neural crest.
Our results will identify a novel post-transcriptional mechanism that acts downstream of signaling systems to
regulate cell state transitions and will shed light on the molecular control of early craniofacial development.

## Key facts

- **NIH application ID:** 10426128
- **Project number:** 5F31DE029996-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Jacqueline Copeland
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $20,370
- **Award type:** 5
- **Project period:** 2021-08-21 → 2022-12-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426128

## Citation

> US National Institutes of Health, RePORTER application 10426128, Post-transcriptional regulation of signaling systems during neural crest induction (5F31DE029996-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10426128. Licensed CC0.

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