Melina Apostolatos
Research Mentor(s): Yuji Mishina
Mentor Department: Biological and Material Sciences
Authors: Hiroki Ueharu, Yuji Mishina
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 20
Abstract
The skull is composed of bones and cranial sutures, which serve as niche for skeletal stem cells (SSCs). Craniosynostosis, one of the major congenital diseases affecting the skull shape, is caused by premature suture closure. Excess osteoblast differentiation is thought to be the mechanism for premature suture closure, because the skull is developed through intramembranous ossification, in which SSCs differentiate into osteoblasts. However, it has been reported that human patients with craniosynostosis exhibited cartilage tissues, suggesting that ectopic cartilage-mediated ossification is a possible mechanism for premature suture closure. It is also reported that an expansion of DDR2-expressing (DDR2+) SSC population contributes to ectopic cartilage formation in cranial sutures, leading to craniosynostosis. Therefore, understanding expansion mechanisms of DDR2+ SSCs would provide possible interventions for craniosynostosis. In mice, the posterior frontal (PF) suture closes through endochondral ossification, where cartilage develops before being replaced by bone. Bone morphogenetic protein (BMP) signaling is known to regulate chondrogenesis in general; however, it is unclear how BMP signaling regulates the PF suture development by coordinating DDR2+ SSCs. This study aims to reveal how BMP signaling contributes expansion and differentiation of DDR2+ SSCs during PF suture development. To determine if DDR2+ SSCs receive active BMP signaling at the PF suture, we will make histological sections for the PF sutures at newborn, postnatal day 5 (P5), P7, P9, and P11. DDR2 and phosphorylated SMAD1/5/9 (BMP signaling transducer) will be detected by immunohistochemistry. We will reveal that DDR2+ SSCs with BMP signaling plays a crucial role in the craniofacial development, specifically for the PF suture. The implications of these results can inform therapeutic strategies for craniosynostosis, such as, manipulating antagonists of BMP signaling may delay suture closure in affected individuals. This research not only advances understanding of skull development but also provides new directions for clinical practice.
