Τίτλος:
The Etiology of Cleft Palate Formation in BMP7-Deficient Mice
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Palatogenesis is a complex process implying growth, elevation and fusion of the two lateral palatal shelves during embryogenesis. This process is tightly controlled by genetic and mechanistic cues that also coordinate the growth of other orofacial structures. Failure at any of these steps can result in cleft palate, which is a frequent craniofacial malformation in humans. To understand the etiology of cleft palate linked to the BMP signaling pathway, we studied palatogenesis in Bmp7-deficient mouse embryos. Bmp7 expression was found in several orofacial structures including the edges of the palatal shelves prior and during their fusion. Bmp7 deletion resulted in a general alteration of oral cavity morphology, unpaired palatal shelf elevation, delayed shelf approximation, and subsequent lack of fusion. Cell proliferation and expression of specific genes involved in palatogenesis were not altered in Bmp7-deficient embryos. Conditional ablation of Bmp7 with Keratin14-Cre or Wnt1-Cre revealed that neither epithelial nor neural crest-specific loss of Bmp7 alone could recapitulate the cleft palate phenotype. Palatal shelves from mutant embryos were able to fuse when cultured in vitro as isolated shelves in proximity, but not when cultured as whole upper jaw explants. Thus, deformations in the oral cavity of Bmp7-deficient embryos such as the shorter and wider mandible were not solely responsible for cleft palate formation. These findings indicate a requirement for Bmp7 for the coordination of both developmental and mechanistic aspects of palatogenesis. © 2013 Kouskoura et al.
Συγγραφείς:
Kouskoura, T.
Kozlova, A.
Alexiou, M.
Blumer, S.
Zouvelou, V.
Katsaros, C.
Chiquet, M.
Mitsiadis, T.A.
Graf, D.
Λέξεις-κλειδιά:
cre recombinase; cytokeratin 14; osteogenic protein 1; Wnt1 protein, animal experiment; animal model; animal tissue; article; cell proliferation; cleft palate; controlled study; disease association; embryo; gene deletion; genetic association; in vitro study; loss of function mutation; mouse; nonhuman; pathological anatomy; phenotype; protein expression; protein function; protein protein interaction; signal transduction, Animals; Bone Morphogenetic Protein 7; Cell Proliferation; Cleft Palate; Embryo, Mammalian; Immunohistochemistry; In Situ Hybridization; Mice; Signal Transduction
DOI:
10.1371/journal.pone.0059463
