Molecular signaling along the anterior–posterior axis of early palate development

Abstract

Cleft palate is a common congenital birth defect in humans. In mammals, the palatal tissue can be distinguished into anterior bony hard palate and posterior muscular soft palate that have specialized functions in occlusion, speech or swallowing. Regulation of palate development appears to be the result of distinct signaling and genetic networks in the anterior and posterior regions of the palate. Development and maintenance of expression of these region-specific genes is crucial for normal palate development. Numerous transcription factors and signaling pathways are now recognized as either anterior- (e.g., Msx1, Bmp4, Bmp2, Shh, Spry2, Fgf10, Fgf7, and Shox2) or posterior-specific (e.g., Meox2, Tbx22, and Barx1). Localized expression and function clearly highlight the importance of regional patterning and differentiation within the palate at the molecular level. Here, we review how these molecular pathways and networks regulate the anterior–posterior patterning and development of secondary palate. We hypothesize that the anterior palate acts as a signaling center in setting up development of the secondary palate.

Determinants of orofacial clefting I: Effects of 5-Aza-2′-deoxycytidine on cellular processes and gene expression during development of the first branchial arch

“…Spatially oriented anterior/posterior gene networks have been shown to exist in the developing palate [85]. Indeed, localized expression and function of several anterior- ( Shox2 and Msx1 ) and posterior- ( Barx1 , Meox2 and Tbx22 ) specific transcriptional regulators are thought to be responsible for the anterior-posterior patterning vital to morphogenesis of the secondary palate [86,87].…”

Analysis of human soft palate morphogenesis supports regional regulation of palatal fusion

“…It is likely that the differences in epithelial-mesenchymal interactions in the two regions of the palate are affected by well-documented differences in gene activity in the posterior vs. anterior palatal shelves. For example, in the mouse, the anterior palate expressed higher levels of ligands Fgf10, Wnt5a and Bmp4 as well as transcription factors Shox2 and Msx1 (Bush & Jiang, 2012;Smith et al 2012). In the posterior palate few ligands have been identified yet; however, transcription factors Tbx22, Mn1, Meox, Barx1 are all strongly expressed posteriorly (Bush & Jiang, 2012;Smith et al 2012).…”

“…For example, in the mouse, the anterior palate expressed higher levels of ligands Fgf10, Wnt5a and Bmp4 as well as transcription factors Shox2 and Msx1 (Bush & Jiang, 2012;Smith et al 2012). In the posterior palate few ligands have been identified yet; however, transcription factors Tbx22, Mn1, Meox, Barx1 are all strongly expressed posteriorly (Bush & Jiang, 2012;Smith et al 2012). Recently, a genome-wide profiling experiment was carried out on the anterior and posterior post-fusion palates of E15.5 mice (Iwata et al 2014) (GEO accession number GSE46211).…”

Dynamic 3D tissue architecture directs BMP morphogen signaling duringDrosophilawing morphogenesis

“…One of the best characterized systems of tissue fusion is the palate, the tissue that separates the oral cavity from the nasal cavity and forms the roof of the mouth. During mammalian embryogenesis, palatogenesis is regulated by a network of signaling molecules and transcription factors to tightly regulate cellular processes (6, 12). Many studies, in both humans and mice, have identified transforming growth factor (TGF)-ß3 as a key signaling factor regulating palatal fusion (13-15).…”