Role of Cilia in Mammalian Tooth Patterning

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Cilia are microtubule-based organelles that have long been observed on most mammalian cells. While their presence has been known, their diverse functions in mammalian development and signaling are poorly understood. Cilia have recently been shown to be essential for hedgehog signaling, PDGFRAA signaling and in modulating Wnt responses. Tooth development in mice is initiated during embryogenesis and requires complex signaling between the oral ectoderm and underlying mesenchyme. As development progresses, ectodermal cells contribute to the superficial structures of the tooth including the enamel while the mesenchyme differentiates into many cell types including the dental pulp cells and odontoblasts which secrete dentin below the enamel. Cilia have been identified on the odontoblasts and mice with partial loss of cilia function have defects in the patterning of the teeth suggesting a role for cilia during the patterning and development of the murine dentition. The goal of this application is to investigate cilia function in tooth formation using a conditional allele of the cilia gene Tg737 and an inducible Cre recombinase to disrupt cilia at two distinct stages of tooth development. The role of cilia during tooth initiation and morphogenesis will be investigated by examining the patterning and development of teeth. After cilia disruption, the resulting teeth will be examined using histology and in situ hybridization. Overall the data obtained will provide preliminary to support more detailed studies. PUBLIC HEALTH RELEVANCE: A growing number of pleiotropic syndromes have been associated with mutations in proteins localized to the cilium and/or basal body and defects in tooth number or structure are evident in patients. In order to better understand how cilia/basal body defects lead to alterations in the dentition, additional work is necessary.