Title

Neural Crest Deletion of Dlx3 Leads to Major Dentin Defects through Down-regulation of Dspp

UMMS Affiliation

Department of Cell Biology

Date

4-6-2012

Document Type

Article

Medical Subject Headings

Transcription Factors; Homeodomain Proteins; Dentin; Neural Crest; Odontoblasts

Disciplines

Cell Biology

Abstract

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.

Rights and Permissions

Citation: J Biol Chem. 2012 Apr 6;287(15):12230-40. Epub 2012 Feb 20. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

22351765