Epithelium of the palatal shelf in the vertical direction can be divided into three regions: the medial epithelium, the lateral epithelium, and the MEE. The medial epithelium that covers the medial side of the shelf develops into the pseudocolumnar epithelium of the nasal cavity [3]. Similarly, the lateral epithelium of the palatal shelf becomes squamous oral epithelium that constitutes the ceiling find more of the oral cavity [3]. The epithelium at the tip of

the palatal shelves is the MEE, at which bilateral palatal shelves contact and fuse. Oral epithelium, including the MEE, comprises two layers of epithelia during development, a flat periderm layer and a cuboidal basal cell layer. The surface layer of the periderm forms from the basal cell layer and persists throughout embryogenesis [4]. Moreover, recent findings suggest that proper differentiation of the oral epithelium provides epithelial integrity for palatal elevation, and BLU9931 solubility dmso the loss of epithelial integrity results in ectopic epithelial fusion, leading

to inhibition of palatal shelf elevation. These findings possibly imply human condition of intraoral synechiae associated with the development of cleft palate [5], [6] and [7]. However, mechanisms responsible for this anomaly have not been elucidated, although in mice, the presence of oral epithelial fusion in some mutant mice strains has been reported [8], [9], [10], [11], [12] and [13]. Van der Woude syndrome (VWS; OMIM119300) and popliteal pterygium syndrome (OMIM119500) Rucaparib supplier are characterized by cleft lip and/or palate accompanied by mucosal cyst (referred to as a “pit”) on the lower lip, as well as hyperproliferative epidermis that fails to undergo terminal differentiation to cause soft tissue fusion. Various genomic analyses as well as analyses of various mutant mouse

models have identified the Interferon regulatory factor 6 (IRF 6) gene encoding a helix-turn-helix transcription factor is responsible for a subset of individuals with VWS and popliteal pterygium syndrome [14], [15] and [16]. Irf6 is expressed in the oral epithelium, and its loss of function in mice (Irf6R84C/R84C) is associated with an inhibition of periderm formation and disorganization of the basal cell layer in mice. In the homozygous mutant of Irf6, disruption of keratin localization was observed, along with ectopic expression of E-cadherin on the surface of the epithelium. This ectopic localization has the potential to induce homophilic binding of E-cadherin between epithelia in close proximity, resulting in tissue fusion. Interestingly, this phenotype is also found in the heterozygote model of Irf6(Irf6+/R84C).