# A Tfap2-mediated molecular switch for neural crest induction and specification

> **NIH NIH F31** · CORNELL UNIVERSITY · 2021 · $22,585

## Abstract

PROJECT SUMMARY/ABSTRACT
The neural crest is a multipotent embryonic cell population that gives rise to most of the craniofacial skeleton,
including cartilage, bone and connective tissue. Misregulation of neural crest development results in the vast
majority of the craniofacial malformations and birth defects. Thus, uncovering the molecular and genetic
underpinnings of neural crest formation has important implications for the diagnosis and treatment of these
pathologies. Formation of the neural crest is a multistep process. This process begins with the induction of the
neural plate border, which is a territory of cells that contains precursors of the neural crest, sensory placodes
and central nervous system. Subsequently, during the process of specification, a subset of the cells from the
neural plate border starts to express a combination of genes that is unique to bona fide neural crest cells.
Several transcription factors are used reiteratively during neural crest formation; however, how they are able
perform distinct functions during induction vs. specification is still unclear. One such factor, Tfap2a, has been
shown to have crucial roles in both steps neural crest formation. Tfap2a belongs to the Tfap2 transcription
factor family, consisting of paralogous proteins that may act as homo- or heterodimers to regulate gene
expression. Two other Tfap2 paralogs, Tfap2c and Tfap2b, are co-expressed with Tfap2a at discrete stages of
neural crest formation, during induction and specification, respectively. Preliminary data suggests that these
factors are able to heterodimerize and regulate distinct groups of target genes. We hypothesize that Tfap2
heterodimers are part of a molecular switch to control the transition from induction to specification during
neural crest development. First, Tfap2a cooperates with Tfap2c to mediate the induction of the neural plate
border. Second, Tfap2a switches partners to heterodimerize with Tfap2b and drive expression of bona fide
neural crest genes in a subset of cells within the neural plate border. We will test this model by employing
stage-specific perturbation assays and identifying protein-DNA and protein-protein interactions in developing
avian embryos. Our results will clarify how neural crest identity is progressively defined during development
and shed light on how factors are able to perform distinct functions in different biological contexts throughout
embryonic development.

## Key facts

- **NIH application ID:** 10114909
- **Project number:** 5F31HD097927-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Megan Rothstein
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $22,585
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-08-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114909

## Citation

> US National Institutes of Health, RePORTER application 10114909, A Tfap2-mediated molecular switch for neural crest induction and specification (5F31HD097927-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114909. Licensed CC0.

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