Carson Horky
Research Mentor: Yuji Mishina
Mentor Department: Biological and Material Sciences, Dentistry
Author(s): Carson Horky, Hiroki Ueharu, Yuji Mishina
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 28
Abstract
Craniosynostosis is a congenital disorder resulting from the premature fusion of cranial sutures, the connective tissues located between calvarial bones. Craniosynostosis occurs in approximately 1 in 2,000 live births, and current treatments involve invasive surgeries at the neonatal stage. In pursuit of understanding the mechanisms underlying craniosynostosis, a recent report identified ectopic cartilage-mediated ossification in cranial sutures as a novel mechanism for craniosynostosis. The anterior frontal (AF) suture, frequently involved in craniosynostosis, is derived from cranial neural crest cells (NCCs) during embryonic development. We have reported that augmentation of bone morphogenic protein (BMP) signaling in cranial NCCs in mice (P0-Cre;caBmpr1a) develops ectopic cartilage in the AF suture, followed by ectopic cartilage-mediated ossification that causes craniosynostosis. The long-term goal of this study is to reveal molecular mechanisms underlying ectopic cartilage formation and thereby provide insights into pharmacological preventive methods for craniosynostosis. Our lab recently identified that BMP-induced additional X-chromosome inactivation (XCI) plays a critical role in chondrogenesis in pathological and normal physiological conditions. Therefore, we hypothesize that additional XCI in P0-Cre;caBmpr1a mice develops ectopic cartilage in the AF suture. We investigate Xist, a master regulator for XCI, in the cranial NCCs of the AF suture. RNAscope in situ hybridization will be used to detect Xist lncRNA, and we will visualize Xist RNA (inactive X-chromosomes) under confocal microscopy and quantify cells with/without ectopic XCI in the AF suture. Based on our preliminary data, we expect to observe XCI signals in both male and female samples, suggesting that Xist activity is present in the AF suture, regardless of sex. XCI has been previously understood to occur only in females; however, these findings will demonstrate XCI as a causal mechanism of craniosynostosis and craniofacial development as a whole and reveal potential targets to prevent premature suture fusion.
