# Genetic regulation of embryonic head mesenchyme patterning

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2021 · $376,438

## Abstract

ABSTRACT
The calvaria (upper part of the skull) comprises plates of bone and fibrous joints (sutures and fontanels), and
the balance between the two components is crucial. Craniosynostosis (premature loss of suture(s)) occurs at a
frequency of 1/2000 births, and it leads to a dysmorphic skull that can further affect brain and orofacial
development. Current treatment of craniosynostosis often involves invasive surgeries at young ages, with risks
for significant morbidity and even mortality. Therefore, improving the methods of intervention for this defect is
of great importance to public health. The long-term goal of our research is to obtain comprehensive
understanding of the molecular genetic regulation of calvarial development, which can lead to innovative
strategies to treat and prevent related birth defects.
 During embryonic development, the head mesenchyme primordium of the calvaria completely encases
the brain from early stages. Subsequently, the calvarial bone starts to develop from the mesenchyme on the
lateral sides of the brain just above the eye (`supra-orbital' mesenchyme, SOM), and expands gradually toward
the vertex. In contrast, the mesenchyme positioned at the vertex from the beginning (`early migrating'
mesenchyme, EMM) does not initiate ossficiation, and contributes only to the soft tissue such as the sutures
and the dermis. This spatial restriction in bone formation is crucial to making the properly patterned calvaria
because it allows the vertex to be occupied by sutures and fontanels instead of bone. To date, little is known
about the factors that underlie this regional difference in the developmental program within the head
mesenchyme.
 Based on our preliminary data, we hypothesize that EMM is intrinsically programmed to resist
osteogenic induction, and that LMX1B (LIM homeobox transcription factor 1b) is a key anti-osteogenic factor in
this context. Therefore, the goal of this proposal is to elucidate the molecular mechanism controlling the
osteogenic competence of EMM with a focus on LMX1B. We will define the spatial and temporal specificity of
LMX1B function during calvarial development, and investigate the effect of LMX1B on the function of
osteogenic signals. Furthermore, we will use genome-wide approaches to define the genetic programs specific
to EMM and SOM, and identify Lmx1b-downstream genetic network that regulates this patterning of the head
mesenchyme.
 The outcome of our research will provide crucial insights into the regulation of early stages of calvarial
development and identify novel mechanisms and players that can contribute to the pathogenesis of
craniosynostosis.

## Key facts

- **NIH application ID:** 10085577
- **Project number:** 5R01DE026798-05
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Juhee Jeong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,438
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085577

## Citation

> US National Institutes of Health, RePORTER application 10085577, Genetic regulation of embryonic head mesenchyme patterning (5R01DE026798-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10085577. Licensed CC0.

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