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

> **NIH NIH K99** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2021 · $69,595

## 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 result in many cranial NC-derived
craniofacial birth defects including craniosynostosis, 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.
 Under the support of this parent award, I have made significant progress toward understanding
the mechanisms of BMP signaling underlying cranial NC EMT and migration. My preliminary results
suggest that BMP signaling peaks during cranial NC cells during EMT, whereas analysis of fixed
sections suggest that signaling level are reduced at earlier (during specification) and later (during
migration) stages (Piacentino et al., 2021). To understand the role of BMP signaling during this
phase, I have inhibited BMP signaling using a dominant negative Type I BMP receptor (dnBMPR1A)
and demonstrated that BMP signaling is essential for cranial NC migration, independent of
specification or delamination. Furthermore, I have identified and validated novel targets of BMP
signaling using a comparative transcriptome profiling approach (Piacentino et al., 2021).
 Unfortunately, the COVID-19 pandemic led to university closures and research restrictions that
have severely delayed my career development. While I have remained productive and have
published results toward the goals of the original proposal (Piacentino et al., 2021), and have
identified a novel endocytic mechanism that regulates BMP signaling in cranial NC cells (Piacentino
et al., 2020) [Preprint], pandemic setbacks have prevented me from completing the training outlined
in my initial Aims. A funding extension will allow me to complete these projects and gain critical
training in 1) live time-lapse imaging to carefully examine BMP signaling dynamics in vivo, 2)
chromatin-immunoprecipitation (ChIP) experiments to identify direct versus indirect targets of BMP
signaling, and 3) co-immunoprecipitation (co-IP) experiments essential to identify the binding partners
of the BMP target genes, Id1/2/3/4. This training is essential for me to gain the skills necessary to
establish a strong independent research program that will make lasting impacts on the field of BMP
signaling in craniofacial development.

## Key facts

- **NIH application ID:** 10448701
- **Project number:** 3K99DE029240-02S1
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael Louis Piacentino
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $69,595
- **Award type:** 3
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448701

## Citation

> US National Institutes of Health, RePORTER application 10448701, Characterizing the neural crest response to BMP signaling through gastrulation and neurulation (3K99DE029240-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10448701. Licensed CC0.

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