Cellular and Molecular Mechanisms of Palatogenesis

Abstract

Palatogenesis involves the initiation, growth, morphogenesis, and fusion of the primary and secondary palatal shelves from initially separate facial prominences during embryogenesis to form the intact palate separating the oral cavity from the nostrils. The palatal shelves consist mainly of cranial neural crest-derived mesenchyme cells covered under a simple embryonic epithelium. Growth and patterning of the palatal shelves are controlled by reciprocal epithelial-mesenchymal interactions regulated by multiple signaling pathways and transcription factors. During palatal shelf outgrowth, the embryonic epithelium develops a “teflon” coat consisting of a single, continuous layer of periderm cells that prevents the facial prominences and palatal shelves from forming aberrant inter-epithelial adhesions. Palatal fusion involves not only spatiotemporally-regulated disruption of the periderm but also dynamic cellular and molecular processes that result in adhesion and intercalation of the palatal medial edge epithelia to form an inter-shelf epithelial seam, and subsequent dissolution of the epithelial seam to form the intact roof of the oral cavity. The complexity of regulation of these morphogenetic processes is reflected by the common occurrence of cleft palate in humans. This review will summarize major recent advances and discuss major remaining gaps in the understanding of cellular and molecular mechanisms controlling palatogenesis.

Sonic Hedgehog regulation of Foxf2 promotes cranial neural crest mesenchyme proliferation and is disrupted in cleft lip morphogenesis

“…*P<0.05 (two-tailed t-test). fusion of facial growth centers that are largely composed of cNCCderived mesenchyme (Jiang et al, 2006;Lan et al, 2015).…”

“…Morphogenesis of the upper lip and palate requires orchestrated growth and fusion of embryonic facial growth centers (Jiang et al, 2006;Lan et al, 2015). Epithelial-mesenchymal cross-talk that drives cellular proliferation and tissue outgrowth is required for closure of both the upper lip and palate.…”

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

“…In mammals, palatal shelves arise from the oral side of the maxillary prominences during embryogenesis and initially grow downward, flanking the developing tongue (Bush and Jiang, 2012;Lan et al, 2015). At a specific developmental stage, the palatal shelves reorient to the horizontal position above the tongue, grow towards the midline and subsequently fuse with each other to form the roof of the oral cavity.…”

“…Concurrent to palate development, the surrounding craniofacial structures undergo significant growth and morphogenesis. Cleft palate could result from intrinsic defects in palatal shelf growth, elevation or fusion, or from failure of the palatal shelves to contact each other at the right developmental stage due to malformation of surrounding structures (Bush and Jiang, 2012;Gritli-Linde, 2007;Hilliard et al, 2005;Lan et al, 2015). Although extensive gene knockout studies in mice in the last 25 years have shown that all major signaling pathways, including Bmp, Fgf, Notch, Shh, Tgfβ and Wnt pathways, play crucial roles in palate development, mutations in known palate development regulators have been found in <30% of cleft palate patients (Bush and Jiang, 2012;Gritli-Linde, 2007;Hilliard et al, 2005;Lan et al, 2015;Moore and Persaud, 1998).…”

Frontonasal Dysplasia: Towards an Understanding of Molecular and Developmental Aetiology

“…The fusion process is best characterised in the formation of the secondary palate where individual epithelial cells make an initial contact through extension of cell surface protrusions known as filopodia [Taya et al, 1999]. Following this initial contact, opposing epithelial surfaces make direct contact, forming a transient bi-epithelial seam which is itself removed through a combination of programmed cell death and conversion of epithelial cells into mesenchyme via epithelial to mesenchymal transformation [Xu et al, 2006;Ke et al, 2015;Lan et al, 2015]. Following successful fusion, the previously separate mesenchymal populations become united as a single continuous population.…”