# Genetic Regulatory Network in Craniofacial Development

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $517,572

## Abstract

Title
Genetic Regulatory Network in Craniofacial Development
Abstract
This proposal continues our efforts to decipher the skeletogenic signaling network underlying craniofacial
development and disease. The craniofacial skeleton consists of viscerocranium and neurocranium, which is
subdivided into the calvarium and chondrocranium. During development of the calvarium, cranial sutures serve
as the growth center for skeletogenesis. Defects in suture morphogenesis resulting in premature closure cause
craniosynostosis, a devastating childhood disease affecting 1 in ~2,500 individuals. Although human genetic
analyses have identified genes associated with the pathogenesis, little is known about the regulation of suture
closure essential for development of a healthy skull. In the previously proposed investigation, we have
elucidated the mechanisms by which Axin2 regulates suture morphogenesis through modulations of Wnt and
downstream signaling pathways. The crosstalk of BMP and FGF signaling plays a pivotal role in Wnt-mediated
craniofacial bone development. Furthermore, skeletal stem cells residing in the suture mesenchyme have been
successfully identified and isolated in our laboratory. This suture stem cell (SuSC) population is responsible for
calvarial development in infants as well as homeostatic maintenance in adults. Upon injury, the dormant
SuSCs respond quickly and contribute directly to bone repair in a cell autonomous fashion. In vivo clonal
analysis demonstrates calvarial bone regeneration at a single cell level. Implantation of SuSCs to an injured
site shows not only long-term survival but also facilitation of bone healing via direct engraftments in which the
implanted stem cells give rise to osteogenic cell types in replacement of the damaged tissue. The newly
discovered SuSCs thus provides an outstanding opportunity to gain novel insights into etiology of
craniosynostosis. In this proposal, we continue our in-depth evaluations of SuSCs by examining their
regulation essential for healthy development and homeostasis of the calvarium. We will concentrate on
elucidation of molecular and cellular mechanisms underlying craniosynostosis caused by dysregulation of
SuSCs.

## Key facts

- **NIH application ID:** 9870920
- **Project number:** 5R01DE015654-12
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Wei Hsu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,572
- **Award type:** 5
- **Project period:** 2006-07-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870920

## Citation

> US National Institutes of Health, RePORTER application 9870920, Genetic Regulatory Network in Craniofacial Development (5R01DE015654-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870920. Licensed CC0.

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