Craniosynostosis is the debilitating precocious ossification of cranial sutures, the fibrous joints between skull bones. 1 in 2500 live births present with synostosis, however, nothing is known about the dynamic cell behaviors underlying calvarial growth and suture formation. Skull defects or damage, such as synostosis or cancer, respectively, are challenging to treat, requiring several reconstructive surgeries. Understanding the morphogenesis of the skull vault may therefore benefit the development of clinical treatment plans and improve faithful skull reconstruction. My recent work shows that the Fuz mutant mouse is a novel model for syndromic craniofacial defects, including craniosynostosis. Here I plan, firstly, to investigate the cause of synostosis in the Fuz mutant using expression, osteogenic and cell mixing analyses. Subsequently, I will utilize a cell biological approach to categorize dynamic cellular behaviors of growing calvarial bones in wildtype and mutant animals. Utilizing fluorescent reporter mouse lines I will perform live imaging analyses of calvarial cells during skull morphogenesis and determine the cell behavior defects underlying craniosynostosis in the Fuz mutant.
The Aims proposed here will comprise the first cell biological analysis of skull morphogenesis and will ultimately help determine the necessary modes of cellular behaviors required to drive apical movement of the calvarial bones.

Public Health Relevance

Craniosynostosis is a disease characterized by premature fusion of the skull bones, which causes severe facial disfigurement and mental retardation. The aim of this project is to understand the cell biological aspects of skull growth in normal and pathogenic contexts to better inform clinical treatment plans and future regenerative medical approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DE023272-02
Application #
8580525
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2012-12-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
2
Fiscal Year
2014
Total Cost
$52,990
Indirect Cost
Name
University of Texas Austin
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Tabler, Jacqueline M; Bolger, TriĆ³na G; Wallingford, John et al. (2014) Hedgehog activity controls opening of the primary mouth. Dev Biol 396:1-7
Tabler, Jacqueline M; Barrell, William B; Szabo-Rogers, Heather L et al. (2013) Fuz mutant mice reveal shared mechanisms between ciliopathies and FGF-related syndromes. Dev Cell 25:623-35