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Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.

Abstract：

:Congenital bony syngnathia, a rare but severe human birth defect, is characterized by bony fusion of the mandible to the maxilla. However, the genetic mechanisms underlying this birth defect are poorly understood, largely due to limitation of available animal models. Here we present evidence that transgenic expression of Bmp4 in neural crest cells causes a series of craniofacial malformations in mice, including a bony fusion between the maxilla and hypoplastic mandible, resembling the bony syngnathia syndrome in humans. In addition, the anterior portion of the palatal shelves emerged from the mandibular arch instead of the maxilla in the mutants. Gene expression assays showed an altered expression of several facial patterning genes, including Hand2, Dlx2, Msx1, Barx1, Foxc2 and Fgf8, in the maxillary and mandibular processes of the mutants, indicating mis-patterned cranial neural crest (CNC) derived cells in the facial region. However, despite of formation of cleft palate and ectopic cartilage, forced expression of a constitutively active form of BMP receptor-Ia (caBmprIa) in CNC lineage did not produce the syngnathia phenotype, suggesting a non-cell autonomous effect of the augmented BMP4 signaling. Our studies demonstrate that aberrant BMP4-mediated signaling in CNC cells leads to mis-patterned facial skeleton and congenital bony syngnathia, and suggest an implication of mutations in BMP signaling pathway in human bony syngnathia.

journal_name

Dev Biol

journal_title

Developmental biology

authors

He F,Hu X,Xiong W,Li L,Lin L,Shen B,Yang L,Gu S,Zhang Y,Chen Y

doi

10.1016/j.ydbio.2014.04.013

subject

Has Abstract

pub_date

2014-07-15 00:00:00

pages

170-81

issue

2

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(14)00220-6

journal_volume

391

pub_type

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