Project description:Little is known about the role of cell-cell adhesion in the development of mineralized tissues. Here we report that PERP, a tetraspan membrane protein essential for epithelial integrity, is a critical regulator of enamel formation. Perp is necessary for proper cell attachment and gene expression during tooth development, and its expression is controlled by P63, a master regulator of stratified epithelial development. During enamel formation, PERP is localized to the interface between the enamel-producing ameloblasts and the stratum intermedium (SI), a layer of cells subjacent to the ameloblasts. Perp-null mice display dramatic enamel defects, which are caused, in part, by the detachment of ameloblasts from the SI. Microarray analysis comparing gene expression in teeth of wild-type and Perp-null mice identified several differentially expressed genes during enamel formation. Analysis of these genes in ameloblast-derived LS8 cells upon knock down of PERP confirmed the role for PERP in the regulation of gene expression. Together, our data show that PERP is necessary for the integrity of the ameloblast-SI interface and that the lack of Perp causes downregulation of genes that are critical for proper enamel formation. Two-condition experiment, RNA isolated from WT vs. Perp-null lower 1st molars. Biological replicates: 3 control replicates, 3 mutant replicates.
Project description:Tooth morphogenesis depends on reciprocal interactions between the dental epithelium and neural crest-derived mesenchyme. ALX1 is a paired-like homeodomain transcription factor implicated in craniofacial development, yet its molecular function during tooth development remains poorly understood. To investigate the transcriptional changes associated with loss of Alx1 during early odontogenesis, we performed bulk RNA sequencing of upper incisor tissues isolated from embryonic day 13.5 (E13.5) neural crest-specific Alx1 conditional knockout mice (Wnt1-Cre;Alx1 flox/flox) and littermate wild-type controls. This dataset provides a comprehensive transcriptomic resource for identifying genes and signaling pathways regulated by Alx1 during early upper incisor development.
