Closing the Gap: Mouse Models to Study Adhesion in Secondary Palatogenesis

Abstract

Secondary palatogenesis occurs when the bilateral palatal shelves (PS), arising from maxillary prominences, fuse at the midline, forming the hard and soft palate. This embryonic phenomenon involves a complex array of morphogenetic events that require coordinated proliferation, apoptosis, migration, and adhesion in the PS epithelia and underlying mesenchyme. When the delicate process of craniofacial morphogenesis is disrupted, the result is orofacial clefting, including cleft lip and cleft palate (CL/P). Through human genetic and animal studies, there are now hundreds of known genetic alternations associated with orofacial clefts; so, it is not surprising that CL/P is among the most common of all birth defects. In recent years, in vitro cell-based assays, ex vivo palate cultures, and genetically engineered animal models have advanced our understanding of the developmental and cell biological pathways that contribute to palate closure. This is particularly true for the areas of PS patterning and growth as well as medial epithelial seam dissolution during palatal fusion. Here, we focus on epithelial cell-cell adhesion, a critical but understudied process in secondary palatogenesis, and provide a review of the available tools and mouse models to better understand this phenomenon.

Targeting YOD1 by RNA Interference Inhibits Proliferation and Migration of Human Oral Keratinocytes through Transforming Growth Factor-β3 Signaling Pathway

“…Our previous study has identified YOD1 as a possible susceptibility gene for NSCL/P [ 28 ]. Cell proliferation and migration have been shown to play an important role in the formation of the facial structures [ 29 , 30 ]. Therefore, our data suggest that the inhibition of cell proliferation and migration caused by YOD1 siRNA may be associated with the occurrence and development of NSCL/P.…”

Unmasking familial CPX by WES and identification of novel clinical signs

“…Missense variants were considered as possibly pathogenic only if predicted to be possibly/probably damaging in at least three out of seven, seven variant in silico classifiers (Sift, Polyphen, LRT, Mutation taster, Mutation assessor, FATHMM, DEOGEN). We considered a list of 89 genes implicated in both syndromic and non‐syndromic CLP (Stanier & Moore, ), nsCLP candidate genes (Leslie & Murray, ) and a selection of CLP candidate genes that we gathered from publications (Conte et al, ; Jugessur, Farlie, & Kilpatrick, ; Kousa, Mansour, Seada, Matoo, & Schutte, ; Lough, Byrd, Spitzer, & Williams, ) including recently confirmed CLP genes such as ARHGAP29 (Leslie et al, ) and GRHL3 (Peyrard‐Janvid et al, ). Gene list is available upon request.…”

Foxg1Organizes Cephalic Ectoderm to Repress Mandibular Fate, Regulate Apoptosis, Generate Choanae, Elaborate the Auxiliary Eye and Pattern the Upper Jaw

“…Additionally, by E12.5 the murine oral epithelium has normally generated a specialized transient superficial cellular population, the periderm, thought to act as a protective barrier that inhibits potentially pathological adhesions between otherwise immature, adhesion-competent epithelia (139)(140)(141)(142)(143). SEM micrographs of the periderm of the rostral secondary palatal shelf of Foxg1 -/-embryos at higher magnification showed an epithelial layer wherein the cellular size, directionality and orientation appears coordinated and uniform while SEM micrographs of comparable periderm of mutant embryos evinced cells that were distinctly flatter, less elongate, and less uniform in directionality (compare Figures 4C', D').…”