Funding outcome

Postnatal skull growth occurs primarily at sutures, fibrous connections between skull bones. Sutures enable the translation of mechanical pressure from the growing brain into signals for stem cell differentiation to form new bone. In humans, they eventually fuse (suture obliteration). Craniosynostosis is premature suture obliteration, which is associated with a lopsided skull. Currently, we lack a good understanding of how mechanical cues translate into bone growth and what keeps sutures patent. BMP2 has been linked to bone formation and increased risk for synostosis, but its role in sutures is less clear. We know BMP signalling promotes osteogenesis, and unfused (patent) sutures are maintained with BMP antagonists. Last summer, I discovered stronger BMP2 expression in sutures after versus during growth. This suggests a role for BMP2 in suture maintenance rather than just bone formation. This discovery provides a novel angle to study suture patency. I hypothesize that BMP2 has a biphasic role in sutures: an early role to establish the suture and a later role in suture maintenance by inhibiting suture obliteration. This summer, I propose a detailed craniofacial characterization of BMP2 neural crest knockout mice. I aim to identify structures requiring BMP2 to elucidate cellular processes dependent on BMP2. I will describe BMP2 in suture establishment, growth, maintenance, and mechanical force integration. To assess if/how BMP2 directly affects bone formation, I will culture BMP2-deficient osteoblast precursors to assess molecular changes in bone formation. This project allows a detailed investigation of molecular and cellular events in suture establishment and maintenance.