# Characterizing the neural crest response to BMP signaling through gastrulation and neurulation

> **NIH NIH K99** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $163,620

## Abstract

PROJECT SUMMARY
 The cranial neural crest (NC) contributes to the formation of many craniofacial structures including the
bones and cartilage of the face, tooth dentin and peripheral ganglia. Cell signaling regulates different aspects
of cranial NC specification, epithelial-to-mesenchymal transition (EMT) and differentiation and disruptions in
this developmental program results in many cranial NC-derived craniofacial birth defects including
craniosynestosis, Treacher Collins and CHARGE syndromes, and cleft palate. BMP signaling plays a crucial
role during the specification and differentiation of cranial NC, and more recently, BMP signaling was shown to
control cranial NC EMT. A mechanistic understanding of the role of BMP signaling during cranial NC
development is essential to develop novel preventative and therapeutic measures against craniofacial
defects.
 This proposal will determine the molecular mechanism of BMP gradient formation in the chick
gastrula, and how this gradient regulates the formation of cranial cell types including neural, cranial NC,
placode and epidermal fates. These experiments will use in vivo and in silico approaches to test the
hypothesis that extracellular BMP ligands are produced primarily by the cranial NC and are actively shuttled
over long distances to signal most strongly in the nonneural ectoderm. Next, quantitative expression analysis
and live imaging will be used to establish the timeline of BMP signaling during gastrulation and neurulation,
and analysis of the resulting datasets will determine population- and single-cell-level responses to BMP
signals. Differences in signal timing and strength will then be correlated with direct input into different target
genes. Finally, the role of BMP target genes Id1/2/3/4 and Fibin during cranial NC EMT will be investigated
using in vivo functional analyses. Together, the results of these aims will provide a comprehensive
understanding of the regulation and roles of BMP signaling events during early cranial NC development.
 In addition to identifying targets for translational avenues to prevent craniofacial birth defects, the
mentored phase of this proposal will provide Dr. Michael Piacentino with necessary training as he prepares to
begin his independent career. Dr. Marianne Bronner's lab at California Institute of Technology, and his
assembled advisory council, provide the necessary tools, expertise, and training environment to efficiently
execute the proposed aims and establish Dr. Piacentino's independence. This training will be instrumental as
Dr. Piacentino begins his independent research program and will provide the experience needed to make
lasting impacts on the field of BMP signaling during craniofacial development.

## Key facts

- **NIH application ID:** 10000879
- **Project number:** 5K99DE029240-02
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael Louis Piacentino
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,620
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000879

## Citation

> US National Institutes of Health, RePORTER application 10000879, Characterizing the neural crest response to BMP signaling through gastrulation and neurulation (5K99DE029240-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000879. Licensed CC0.

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