# Cellular determinants of cardiopharyngeal multipotency and early fate choices

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2022 · $573,039

## Abstract

SUMMARY
Prevalent congenital diseases, including the Di George/22q11DS, Noonan and related syndromes, present with
both cardiac defects and craniofacial dysmorphism. The 22q11 Deletion Syndrome arises from eponymous
deletions that cause TBX1 haploinsufficiency, while Noonan and related syndromes are RASopathies that affect
the RAS-MAPK signaling pathway. However, understanding the etiology of combined cardio-craniofacial
defects requires insights into the cellular and developmental contexts of gene function. In early amniote
embryos, the second heart field (SHF) and branchiomeric/pharyngeal head muscles emerge from a common
population of multipotent progenitors in the cardiopharyngeal mesoderm. TBX1 is thought function in
cardiopharyngeal progenitors, to control both pharyngeal myogenesis and SHF development, and interact with
Fibroblast Growth Factor (FGF)-MAPK signaling during heart development, highlighting the importance of
studying Tbx1 and FGF-MAPK signaling in the cellular context of early cardiopharyngeal development.
The tunicate Ciona emerged as a simple and powerful chordate model to study early cardiopharyngeal
development, with high spatial and temporal resolution. In Ciona, four multipotent cardiopharyngeal
progenitors undergo stereotyped migration and cell divisions, producing distinct first and second cardiac, and
pharyngeal muscle lineages that deploy gene networks conserved with vertebrates. Leveraging the unique
strengths of the Ciona system, and extensive previous work using lineage-specific perturbations, including
CRISPR/Cas9-mediated mutagenesis, quantitative imaging, and multiplexed single cell genomics methods,
this proposal will first explore the establishment of spatial patterns. The proposed work will address how a
dynamic cardiopharyngeal niche helps polarize MAPK signaling and Tbx1/10 activation; how an intrinsic
determinant of mitotic spindle positioning, the RhoGAP Depdc1, helps progenitors orient their divisions with
regards to the niche, and analyze the molecular basis for the antagonism between MAPK signaling and the
early heart program. Second, this proposal will explore the temporal dynamics underlying transitions between
cardiopharyngeal states, by studying how de novo gene expression and fate choices are coupled with cell
divisions, and how transcriptome changes in maturing progenitors determine the competence of
cardiopharyngeal progenitors to form heart and pharyngeal muscle precursors. Completion of this ambitious
proposal will yield far-reaching insights into emerging concepts of broad significance for cardiovascular
developmental and stem cell biology.

## Key facts

- **NIH application ID:** 10470093
- **Project number:** 5R01HL108643-11
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Lionel Christiaen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $573,039
- **Award type:** 5
- **Project period:** 2011-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470093

## Citation

> US National Institutes of Health, RePORTER application 10470093, Cellular determinants of cardiopharyngeal multipotency and early fate choices (5R01HL108643-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10470093. Licensed CC0.

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