Neural crest deletion of Dlx3 leads to major dentin defects through down-regulation of Dspp.

[dentin dysplasia]

During development , Dlx 3 is expressed in ectodermal appendages such as hair and teeth . Thus far , the evidence that Dlx 3 plays a crucial role in tooth development comes from reports showing that autosomal dominant mutations in DLX 3 result in severe enamel and dentin defects leading to abscesses and infections . However , the normal function of DLX 3 in odontogenesis remains unknown . Here , we use a mouse model to demonstrate that the absence of Dlx 3 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 Dlx 3 . Using ChIP-seq , we further demonstrate the direct binding of Dlx 3 to the Dspp promoter in vivo . Luciferase reporter assays determined that Dlx 3 positively regulates Dspp expression . This establishes a regulatory pathway where the transcription factor Dlx 3 is essential in dentin formation by directly regulating a crucial matrix protein .