Molecular contribution to cleft palate production in cleft lip mice

Abstract

Cleft palate following cleft lip may include a developmental disorder during palatogenesis. CL/Fr mice fetuses, which develop cleft lip and palate spontaneously, have less capability for in vivo cell proliferation in palatal mesenchyme compared with CL/Fr normal fetuses. In order to know the changes of signaling molecules contributing to cleft palate morphogenesis following cleft lip, the mRNA expression profiles were compared in palatal shelves oriented vertically (before elevation) in CL/Fr fetuses with or without cleft lip. The changes in mRNA profile of cleft palate morphogenesis were presented in a microarray analysis, and genes were restricted to lists contributing to cleft palate development in CL/Fr fetuses with cleft lip. Four candidate genes (Ywhab, Nek2, Tacc1 and Frk) were linked in a gene network that associates with cell proliferation (cell cycle, MAPK, Wnt and Tgf beta pathways). Quantitative real-time RT-PCR highlighted the candidate genes that significantly changed in CL/Fr fetuses with cleft lip (Ywhab, Nek2 and Tacc1). The results of these molecular contributions will provide useful information for a better understanding of palatogenesis in cleft palate following cleft lip. Our data indicated the genetic contribution to cleft palate morphogenesis following cleft lip.

Epidemiology, Etiology, and Treatment of Isolated Cleft Palate

“…They are composed of cranial neural crest-derived mesenchymal cells and mesoderm-derived endothelial cells, which together are covered by pharyngeal ectoderm-derived epithelial cells (Iwata et al, 2011 ; Hill et al, 2015 ). Normal development of the palate depends on proper migration, growth, differentiation, and apoptosis of these cells, and occurs in three major stages: vertical growth of the shelves down toward the sides of the tongue, elevation of the palatal shelves to acquire a horizontal position as the mandible lengthens, and fusion of the palatal shelves to form the transient midline epithelial seam, which ultimately undergoes epithelial to mesenchymal transition (Mossey et al, 2009 ; Sasaki et al, 2014 ). Cleft palate can arise due to an error in any of these stages, which many studies have demonstrated in mouse models.…”

Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout

“…The initiation of primary palate development in mouse starts from day E11.5 and ends at day E17 with complete fusion of the palatal shelf 25 . The whole process is composed of three major stages: 1) vertical growth of the shelves away from the maxilla along the side of the tongue, 2) elevation of palatal shelves to acquire a horizontal position above the tongue, 3) formation of the midline epithelial seam (MES) by fusion of the medial edge epithelia (MEE) of the two opposing palatal shelves at the midline of nasal oral cavity 26–29 . In order to investigate where Arl15 gene is expressed during palatogenesis, we used a tm1b lacZ Arl15 reporter mouse line, collected embryos at E12.5 and stained with x‐gal, and found positive staining in primordium primary palate, cartilage primordium of nasal septum and the tongue as indicated by arrows (Figure 4).…”

Reduction in Wnt9b and associated gene expression in the embryonic midface of CL/Fr mice with heritable cleft lip and palate

“…[23] Furthermore, proliferation of the palatal mesenchyme was reduced in the palatal shelves of CL/Fr mice. [37,38] Our initial qRT-PCR studies on the most highly upregulated gene in the array, Sst ( Table 1) showed a 1.72-fold up-regulationin CL/Fr tissues ( Figure 5). Sst is a growth hormone-inhibiting hormone with many known functions, which include inhibiting cell proliferation and promoting apoptosis.…”