Investigating the emergence and signaling functions of the periosteal dura mater in calvarial development
Active Project Grant Awarded Last action
- Award ID
- F31DE036486
- Recipient
-
University Of California, LOS Angeles UEI RN64EPNH8JC6
- Awarding agency
-
National Institute of Dental and Craniofacial Research
National Institutes of Health, Department of Health and Human Services
- Obligated
- $43,858
Award facts
- Assistance listing
- 93.121 Oral Diseases and Disorders Research
- Completion date 0% complete
- Place of performance
- Los Angeles, CA 90095, USA
Award details come from USAspending.gov.
Description
- Abstract
- Proper craniofacial development requires sustained growth at cranial sutures, the fibrous joints that separate calvarial bones. Craniosynostosis, the premature fusion of these sutures, restricts skull expansion and impairs brain growth. Although ~20% of cases arise from known genetic causes, the remaining ~80% of nonsyndromic cases lack clear etiologies, underscoring major gaps in our understanding of the cellular and tissue-level mechanisms that maintain suture patency. Sutures form within a complex microenvironment composed of multiple mesenchymal tissues with distinct transcriptional identities. Among these, the dura mater, the outermost meningeal layer, has emerged as a key but poorly understood regulator of suture biology. Recent work from the farmer lab and others has begun to define the cellular architecture of the dura, including the discovery of a transcriptionally distinct periosteal dura population positioned directly beneath calvarial bones. This subtype expresses chemokines with potential to influence osteogenesis and suture patency, including IGF1.signaling has been implicated in meningeal function and activating mutations in IGF1R cause nonsyndromic craniosynostosis. However, whether periosteal dura-derived IGF1 directly instructs bone growth or suture maintenance has not been tested in vivo. To dissect meninges-calvaria communication with spatial and temporal precision, I will leverage the zebrafish, an emerging model of calvarial development that has multilayered meninges including a periosteal dura mater population and enables exquisite integration of genetic and imaging approaches. I hypothesize that periosteal dura mater development is tightly coupled to calvarial bone formation, and that IGF1-dependent signaling between periosteal dura and calvaria provides a localized, sustained pro- osteogenic CUE required for proper calvarial growth and suture maintenance. This proposal integrates lineage tracing, cellular-resolution spatial transcriptomics, and newly developed genetic tools to manipulatesignaling and model disease-associated IGF1R mutations. Together these studies will resolve the developmental relationship between dura mater and calvaria and define how their signaling interactions establish and preserve suture biology. This work will broaden the conceptual framework for craniosynostosis, reframing IT not solely as a defect intrinsic to the suture mesenchyme, but as a disorder that can arise from disrupted inter-tissue signaling between the meninges and the calvaria.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $43,858 |
Quick answers
Who received award F31DE036486?
F31DE036486 was awarded to University Of California, LOS Angeles by National Institute of Dental and Craniofacial Research (National Institutes of Health) on December 1, 2026.
How much is award F31DE036486 worth?
$43,858 has been obligated on F31DE036486.
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