Homeobox family Hoxc localization during murine palate formation

Congenit Anom (Kyoto). 2016 Jul;56(4):172-9. doi: 10.1111/cga.12153.

Abstract

Homeobox genes play important roles in craniofacial morphogenesis. However, the characteristics of the transcription factor Hoxc during palate formation remain unclear. We examined the immunolocalization patterns of Hoxc5, Hoxc4, and Hoxc6 in palatogenesis of cleft palate (Eh/Eh) mice. On the other hand, mutations in the FGF/FGFR pathway are exclusively associated with syndromic forms of cleft palate. We also examined the immunolocalization of Fgfr1 and Erk1/2 to clarify their relationships with Hoxc in palatogenesis. Some palatal epithelial cells showed Hoxc5 labeling, while almost no labeling of mesenchymal cells was observed in +/+ mice. As palate formation progressed in +/+ mice, Hoxc5, Hoxc4, and Hoxc6 were observed in medial epithelial seam cells. Hoxc5 and Hoxc6 were detected in the oral epithelium. The palatal mesenchyme also showed intense staining for Fgfr1 and Erk1/2 with progression of palate formation. In contrast, the palatal shelves of Eh/Eh mice exhibited impaired horizontal growth and failed to fuse, resulting in a cleft. Hoxc5 was observed in a few epithelial cells and diffusely in the mesenchyme of Eh/Eh palatal shelves. No or little labeling of Fgfr1 and Erk1/2 was detected in the cleft palate of Eh/Eh mice. These findings suggest that Hoxc genes are involved in palatogenesis. Furthermore, there may be the differences in the localization pattern between Hoxc5, Hoxc4, and Hoxc6. Additionally, Hoxc distribution in palatal cells during palate development may be correlated with FGF signaling. (228/250 words) © 2016 Japanese Teratology Society.

Keywords: Eh/Eh mouse; Fgf signaling; Hoxc; cleft palate; palate formation.

MeSH terms

  • Animals
  • Cleft Palate / genetics
  • Cleft Palate / pathology
  • Disease Models, Animal
  • Ectopic Gene Expression
  • Female
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Immunohistochemistry
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Multigene Family
  • Organogenesis* / genetics
  • Palate / embryology*
  • Palate / metabolism*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Transport
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism

Substances

  • Homeodomain Proteins
  • Proliferating Cell Nuclear Antigen
  • Receptor, Fibroblast Growth Factor, Type 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3