# Molecular mechanisms orchestrating EMTs in the cranial neural crest

> **NIH NIH R56** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $363,313

## Abstract

PROJECT SUMMARY
This proposal aims to address an outstanding issue in developmental biology: What cellular and molecular
mechanisms endow immotile cells with the capacity to migrate and ultimately pattern the vertebrate embryo?
Neural crest cells (NCCs) provide an exceptional model in which to address this fundamental question, as they
differentiate to form various cell types including cranial bones and cartilage, sensory neurons, and melanocytes.
Abnormalities in NCC formation are thus responsible for diverse human diseases, such as cancers, craniofacial
anomalies, and disorders of the peripheral nervous system. Initially stationary epithelial cells, premigratory NCCs
undergo an epithelial-to-mesenchymal transition (EMT), which is typified by changes in cell adhesion and
morphology, along with breakdown of extracellular matrix, to become motile. The en masse nature of cranial
NCC EMT requires an extraordinary degree of coordination, but how premigratory NCCs initiate and orchestrate
this transition remains obscure. Our published and preliminary data have begun to bridge this knowledge gap,
revealing the importance of Cadherin-6B (Cad6B) proteolysis during EMT, which reduces cell-cell adhesion to
liberate NCCs but also generates peptides (Cad6B N-terminal fragments, NTFs; Cad6B C-terminal fragment 2,
CTF2) with novel pro-EMT functions. Cad6B NTFs augment protease activity to facilitate degradation of
extracellular matrix substrates, and Cad6B CTF2 modulates expression of critical EMT genes involved in cellular
invasion, as identified by both targeted and global transcriptomics approaches. Herein, we propose to elucidate
how Cad6B proteolytic peptides function in concert to control NCC EMT, using chick cranial NCCs as a unique
in vivo model for EMT that has the advantage of direct translatability to human development. The aims in this
proposal will test the hypothesis that EMT is orchestrated by cadherin peptides with distinct activities and
functions within the premigratory cranial NCC population. To define the role of Cad6B NTFs during NCC EMT
(Aim 1), we will evaluate the interrelationship among NTFs, proteases, and substrates, and determine the
expression and function of NTF binding partners previously obtained via a novel mass spectrometry assay in the
embryo. To investigate the role of Cad6B CTF2 as a transcriptional modulator during NCC EMT (Aim 2), we will
continue characterizing newly identified CTF2 target genes and determine their mechanism of regulation by
CTF2, and use ChIP-seq, followed by CTF2-associated sequence mapping and bioinformatics, to reveal new
target genes and DNA binding motifs important for CTF2-mediated gene expression. Our proposed research is
innovative as it takes a multidisciplinary approach combining embryology, biochemistry, bioinformatics, and
novel microscopic analyses to examine the coordination of EMT in vivo. These studies will have great
significance to the field by providing a heuristic paradigm to tackle ...

## Key facts

- **NIH application ID:** 10214990
- **Project number:** 1R56DE028523-01A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** LISA A TANEYHILL
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,313
- **Award type:** 1
- **Project period:** 2020-08-05 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214990

## Citation

> US National Institutes of Health, RePORTER application 10214990, Molecular mechanisms orchestrating EMTs in the cranial neural crest (1R56DE028523-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10214990. Licensed CC0.

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