Therefore, it is important to identify the regulatory genes that orchestrate these molecular interactions between dental epithelial and mesenchymal cells. We previously performed cDNA subtraction between the mandibles on embryonic day 10.5 and E12.0 to investigate the regulatory genes associated with odontogenesis. Nine highly expressed positive clones from the E10.5 mandible and five highly expressed positive clones from the E12.0 mandible were obtained by colony array screening. The expression of several of these genes is closely associated with the developing tooth germ. Integral membrane protein 2a was one of the highly expressed genes in the E12.0 mandible. The Itm2a gene was originally isolated by a cDNA library subtraction of in vitro cultivated murine mandibular condyles. The Itm2a protein and its related proteins, Itm2b and Itm2c, belong to the BRICHOS superfamily. These Itm2 proteins consist of four regions with distinct properties; the hydrophobic, linker, BRICHOS and C-terminal regions, as do other proteins in the BRICHOS superfamily, and are type II transmembrane proteins. Itm2a bears one BRICHOS domain at the C-terminal extracellular side. The expression of Itm2c is restricted to the brain, whereas Itm2b is ubiquitously expressed. Itm2a is expressed in the developing muscle and in chondrocytes of the resting zone of the murine growth plate. Itm2a is also expressed in mature odontoblasts as well as Tcells and hair follicles. Zatebradine However, the function of Itm2a is so far unknown, except for its potential to regulate chondrogenic and myogenic differentiation. In addition, only a few studies have so far addressed the intracellular localization of Itm2a protein. In the murine thymoma cell line, EL4, the Itm2a protein was observed in large cytoplasmic vesicles, and then translocated to the plasma membrane in the activated cells, whereas Itm2a protein was detected in the nuclei of human uterine Metandienone endometrial stromal sarcoma cells.Thus far, the function, expression pattern and intracellular localization of Itm2a mRNA and protein have not yet been fully elucidated. In this study, the expression patterns of Itm2a mRNA and protein were examined in the course of tooth germ development from initiation to root formation.