# Genetic regulation of embryonic head mesenchyme patterning

> **NIH NIH R56** · NEW YORK UNIVERSITY · 2024 · $366,275

## Abstract

ABSTRACT
The calvaria (upper part of the skull) comprises plates of bone and fibrous joints (sutures and fontanels).
While the bone protects the brain, the sutures contain stem cells for osteoblasts, and thus allow the skull to
grow coordinately with the expanding brain of a child. Craniosynostosis (a premature loss of the suture(s)) is
a major class of human birth defects. It can lead to dysmorphic skull, and further affect brain and orofacial
development. Current treatment for craniosynostosis often involves invasive and repetitive surgeries at young
ages with relatively high rates of complications. Therefore, improving the methods of intervention for this
defect is of great importance to public health.
 The calvaria is made of cells from the neural crest and the mesoderm in embryos. In mice, these cells
form a mesenchyme layer that completely encases the brain soon after mid-gestation (cranial mesenchyme).
The cranial mesenchyme on the apical side of the head (a.k.a. early migrating mesenchyme, EMM) gives rise
to soft tissues such as the sutures, the dermis/hypodermis of the scalp, and the meninges.
 Our previous study has shown that LMX1B (LIM homeobox transcription factor 1b) plays a key role in
suppressing osteogenesis in EMM to allow suture formation. Recently, single cell sequencing and in silico
analyses from our group and others have suggested that EMM contains two populations of intermediate
progenitors: suturodermal progenitors (SDP) with a dual potential for the suture mesenchyme and the
dermis/hypodermis, and common meningeal progenitors (CMP), which contribute to the dura and the
arachnoid layers of the meninges. We found that both SDP and CMP populations were severely decreased in
Lmx1b mutants, whereas cells with a restricted fate were increased and appeared precociously. The goal of
this project is to identify factors underpinning cell fate specification and differentiation in the cranial
mesenchyme, and to utilize this information to generate SDP in vitro from human embryonic stem cells
(hESC). In Aim1. we will determine transcription factors and signaling pathways that regulate cell fate
specification and differentiation in the cranial mesenchyme in vivo. In Aim2, we will determine genetic
regulators that control SDP specification and differentiation in vitro from hESC. The completion of this project
will fill the critical gap in the current knowledge of suturogenesis. Furthermore, our results can facilitate efforts
to use suture stem cells for craniosynostosis treatment, a promising new direction of research in the field.

## Key facts

- **NIH application ID:** 11137238
- **Project number:** 2R56DE026798-06
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Juhee Jeong
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,275
- **Award type:** 2
- **Project period:** 2017-04-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11137238

## Citation

> US National Institutes of Health, RePORTER application 11137238, Genetic regulation of embryonic head mesenchyme patterning (2R56DE026798-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11137238. Licensed CC0.

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