# Characterization of calvarial defects in Marfan syndrome models

> **NIH NIH R03** · NEW YORK UNIVERSITY · 2024 · $161,000

## 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.
Mutations of FBN1, encoding fibrillin-1, underlie several human syndromes affecting cardiovascular, skeletal,
and ocular systems, including Marfan syndrome (MFS). Fibrillins are components of microfibrils in the
extracellular matrix, which provides mechanical supports in the connective tissue. Furthermore, fibrillins can
modulate intercellular signaling by sequestering ligands such as bone morphogenetic protein (BMP) and
tumor growth factor (TGF) β proteins. Craniosynostosis is one of the features associated with FBN1
mutations in humans. However, unlike other MFS defects, it has not received any attention from the
perspective of basic science research, and thus the connection between FBN1 mutations and
craniosynostosis remains poorly understood. In our preliminary study, we have discovered that mouse Fbn1
mutants carrying a MFS mutation have severe deficiency in calvarial sutures at birth, thus establishing a
model to investigate FBN1-associated calvarial defects.
The proposed project will define the role of fibrillin-1 during normal cranial suture development, and
investigate the molecular and cellular mechanism underlying the calvarial defects in Fbn1 mutants. The
specific aims will uncover temporal and spatial specificities of fibrillin-1 function in this context, identify
candidate fibrillin-1-downstream pathways in an unbiased manner, and establish the importance of TGFβ
signaling to the function of fibrillin-1 in suture development. Findings from this project can have a major
impact on both basic science research and translational research involving sutures by providing new
information on crucial factors necessary for suture generation and maintenance.

## Key facts

- **NIH application ID:** 10869053
- **Project number:** 1R03HD114829-01
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Juhee Jeong
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,000
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869053

## Citation

> US National Institutes of Health, RePORTER application 10869053, Characterization of calvarial defects in Marfan syndrome models (1R03HD114829-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869053. Licensed CC0.

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