# Molecular Interactions during Neural Crest Formation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2022 · $483,970

## Abstract

Project Summary/Abstract.
Neural crest cells (NC) are unique to vertebrates, arise early in development, emigrate from the dorsal aspect of
the neural tube, and differentiate into a plethora of derivatives throughout the body, contributing neurons and glia
of the peripheral nervous system, melanocytes, and craniofacial bone and cartilage amongst other derivatives.
Failed NC development is associated with a large number of conditions known as Neurocristopathies, which
include common orofacial clefts, aggressive cancers and rare syndromes. The long term goal of this research
program is to advance our understanding of the earliest signaling events responsible for the formation of the NC.
Currently signaling by WNT, FGF and BMP are amongst a few of key inputs recognized to be critical for the
formation of NC, yet our understanding of the molecular mechanisms by which they execute their effects remain
limited. To improve our knowledge of this events, it is critical to identify the effectors modulated by these pathways
and to characterize their effects. The objectives of this proposal are: 1) to establish and characterize for the
first time the role of TGFb /SMAD2-SMAD3 signaling during early facets of NC formation, prior to their allocation
into the neural tube, migration or differentiation; and 2) to identify the effectors of the WNT and/or TGFb and
characterize their role during early NC formation. Our Hypotheses are that the TGFb /SMAD2-SMAD3 signaling
is required to launch the earliest events in NC formation, and that a combination of TGFb and WNT responsive
molecules direct the specific acquisition of the NC lineage. To address these hypotheses our proposal is guided
by 3 specific aims: 1) to demonstrate the requirement and contribution of the TGFb /SMAD2-SMAD3 signaling
during early facets of NC formation, 2) to identify novel candidate effectors of WNT and/or TGFb and characterize
their specific contributions to the acquisition of the NC fate, and 3) to assess their function in vivo in a vertebrate
embryo. This innovative proposal takes advantage of a robust model of human NC formation based in
pluripotent stem cells and classic chick embryology to, for the first time address the possible contribution of
TGFb signaling (not BMPs) during this process and pursues an integrative approach addressing the
combinatorial signaling of WNT and TGFb. The proposal is significant because the gains in this area will have
impact in key aspects of fate acquisition and differentiation applicable to other cell types, and should improve our
capacity to manage the many pathologies associated with NC.

## Key facts

- **NIH application ID:** 10458050
- **Project number:** 5R01DE017914-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** MARTIN I. GARCIA-CASTRO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $483,970
- **Award type:** 5
- **Project period:** 2007-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458050

## Citation

> US National Institutes of Health, RePORTER application 10458050, Molecular Interactions during Neural Crest Formation (5R01DE017914-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458050. Licensed CC0.

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