RESUMEN
During development, Dlx3 is expressed in ectodermal appendages such as hair and teeth. Thus far, the evidence that Dlx3 plays a crucial role in tooth development comes from reports showing that autosomal dominant mutations in DLX3 result in severe enamel and dentin defects leading to abscesses and infections. However, the normal function of DLX3 in odontogenesis remains unknown. Here, we use a mouse model to demonstrate that the absence of Dlx3 in the neural crest results in major impairment of odontoblast differentiation and dentin production. Mutant mice develop brittle teeth with hypoplastic dentin and molars with an enlarged pulp chamber and underdeveloped roots. Using this mouse model, we found that dentin sialophosphoprotein (Dspp), a major component of the dentin matrix, is strongly down-regulated in odontoblasts lacking Dlx3. Using ChIP-seq, we further demonstrate the direct binding of Dlx3 to the Dspp promoter in vivo. Luciferase reporter assays determined that Dlx3 positively regulates Dspp expression. This establishes a regulatory pathway where the transcription factor Dlx3 is essential in dentin formation by directly regulating a crucial matrix protein.
Asunto(s)
Dentina/patología , Proteínas de la Matriz Extracelular/genética , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Cresta Neural/metabolismo , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Factores de Transcripción/genética , Ameloblastos/metabolismo , Ameloblastos/fisiología , Animales , Secuencia de Bases , Diferenciación Celular , Línea Celular , Esmalte Dental/crecimiento & desarrollo , Esmalte Dental/metabolismo , Dentina/crecimiento & desarrollo , Dentina/metabolismo , Displasia de la Dentina/genética , Displasia de la Dentina/patología , Regulación hacia Abajo , Proteínas de la Matriz Extracelular/metabolismo , Genes Reporteros , Proteínas de Homeodominio/metabolismo , Luciferasas de Renilla/biosíntesis , Luciferasas de Renilla/genética , Mandíbula/metabolismo , Mesodermo/metabolismo , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Odontoblastos/metabolismo , Odontoblastos/fisiología , Fosfoproteínas/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Sialoglicoproteínas/metabolismo , Diente/crecimiento & desarrollo , Diente/metabolismo , Diente/patología , Factores de Transcripción/metabolismoRESUMEN
Estimating tooth age and skeletal age are the two primary methods in age estimation of forensic medicine. But they are often impacted with geographical environment, nutrition, habitation and ethenologic differences, so the accuracy will be reduced, especially to the adult. With the study of telomere, it is certain that the length of the telomere DNA can reflect the cell division and represent the cell lifespan, and it has some pertinence to the age of the donor, so to measure the length of telomere DNA is a new and valuable method for age estimation in the forensic medicine.