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

Abstract

It is essential to complete palate closure at the correct time during fetal development, otherwise a serious malformation, cleft palate, will ensue. The steps in palate formation in humans take place between the 7th and 12th week and consist of outgrowth of palatal shelves from the paired maxillary prominences, reorientation of the shelves from vertical to horizontal, apposition of the medial surfaces, formation of a bilayered seam, degradation of the seam and bridging of mesenchyme. However, in the soft palate, the mechanism of closure is unclear. In previous studies it is possible to find support for both fusion and the alternative mechanism of merging. Here we densely sample the late embryonic-early fetal period between 54 and 74 days post-conception to determine the timing and mechanism of soft palate closure. We found the epithelial seam extends throughout the soft palates of 57-day specimens. Cytokeratin antibody staining detected the medial edge epithelium and distinguished clearly that cells in the midline retained their epithelial character. Compared with the hard palate, the epithelium is more rapidly degraded in the soft palate and only persists in the most posterior regions at 64 days. Our results are consistent with the soft palate following a developmentally more rapid program of fusion than the hard palate. Importantly, the two regions of the palate appear to be independently regulated and have their own internal clocks regulating the timing of seam removal. Considering data from human genetic and mouse studies, distinct anterior-posterior signaling mechanisms are likely to be at play in the human fetal palate.

Fetal Development of the Incisive Canal, Especially of the Delayed Closure Due to the Nasopalatine Duct: A Study Using Serial Sections of Human Fetuses

“…Most of the present specimens were much later or larger than those used by Danescu et al (2015) who published an excellent study of soft palate development. Therefore, rather than palatogenesis, the present study concentrated onto a clear demonstration of anatomy of the nasopalatine duct.…”

“…Epithelial pearls seemed to be classified into three types: (1) midline pearls originating from the midline epithelial seam of the palate; (2) paramedian pearls derived from the oral epithelium at Albrecht's incisive suture; and (3) lateral pearls arising from the dental lamina of all tooth buds. However, previous descriptions of epithelial pearls did not distinguish paramedian from other median and lateral pearls (Kitamura, 1991;Arnold et al, 1998;Danescu et al, 2015). Another disturbing factor in the fetal anterior palate is the developing vomer, as its lower part is likely to form a canal or space immediately above the incisive bone (Hansen et al, 2004).…”

Development of the squamate naso-palatal complex: detailed 3D analysis of the vomeronasal organ and nasal cavity in the brown anole Anolis sagrei (Squamata: Iguania)

“…In fact, the presumptive vestibulum containing the nasal plug at stages 6 and 7 of the brown anole (Figs. 3 B and S 2 A) resembles a multilayered medial edge epithelial seam in the human embryonic soft palate (see [ 79 ]), although in the anole the basal layer, which forms the walls of the future vestibulum, can easily be distinguished. Distribution of the nasal plug is restricted to the vestibulum in later embryonic life [ 22 , 71 , 72 ].…”

Facial Genetics: A Brief Overview

“…The facial processes fuse at different times; maxillary – 6 weeks, upper lip – 8 weeks and palate – 12 weeks ( O’Rahilly, 1972 ; Danescu et al, 2015 ). Molecular studies have shown that the growth, structure and patternation of the facial primordia is controlled by a series of complex interactions that involves many factors such as fibroblast growth factors, sonic hedgehog proteins, bone morphogenetic proteins, homeobox genes Barx1 and Msx1 , the distal-less homeobox ( Dlx ) genes, and local retinoic acid gradients ( Barlow et al, 1999 ; Hu and Helms, 1999 ; Lee et al, 2001 ; Ashique et al, 2002 ; Mossey et al, 2009 ; Marcucio et al, 2015 ; Parsons et al, 2015 ).…”