The Roles of SATB1 on the Morphogenesis of Secretory Ameloblasts

Objectives: Enamel, the hardest tissue in the human body, protects teeth from wear, caries progression, and fracture. Enamel formation starts with depositing the full thickness of enamel matrix proteins into enamel space by secretory ameloblasts (SABs) through their apical cytoplasmic protrusion, so called Tomes’ processes. Special AT-rich sequence-binding protein 1 (SATB1), a higher-order chromatin organizer, was found to be spatially and temporarily upregulated in preameloblasts. The enamel matrix structure and SAB morphology including cell polarity, tight junction complex and Tomes’ processes were compromised in the Satb1 null mouse model. Understanding the molecular mechanisms that contribute to the polarization and secretory trafficking of amelogenins allow us to someday be able to regenerate enamel-forming ameloblasts and enamel.
Methods: The enamel density and enamel rod structure of P13 Satb1^+/+ and Satb1^-/- mouse teeth were analyzed through X-ray imaging and scanning electron microscope. Hemimandibles from P1 and P5 Satb1^+/+ and Satb1^-/- mice were dissected, paraffin-embedded and processed for histological and immunochemistry analyses, and actin filament labeling to determine the effects of SATB1 on ameloblast polarity, actin filament assembly and secretory vesicle trafficking.
Results: In the mice with the deletion of Satb1 gene, poorly mineralized enamel was developed and enamel rods were disorganized. Secretory ameloblasts (SABs) in Satb1^-/- mice were significantly shorter in length and lost Tomes’ processes and terminal actin filament band that appeared at the apical pole of wild type (wt) SABs. A majority of amelogenins remained in Satb1^-/- SABs instead of depositing to enamel matrix, resulting in a thin, hypomineralized and non-prismatic enamel.
Conclusions: Through regulating the expression of a set of genes associated with SAB apical polarity, F-actin assembly and vesicle packaging, SATB1 is critical for ameloblastic vesicle trafficking to enamel matrix space. This study suggests the roles of SATB1 on ameloblast morphogenesis and its potential application in functional ameloblast regeneration.