期刊
CELLS TISSUES ORGANS
卷 179, 期 4, 页码 146-157出版社
KARGER
DOI: 10.1159/000085950
关键词
hedgehog; sonic hedgehog; Meckel's cartilage; FGF8; mutant mouse; agnathia-holoprosencephaly syndrome
资金
- NIDCR NIH HHS [DE011942] Funding Source: Medline
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE011942] Funding Source: NIH RePORTER
The hedgehog (Hh) signaling pathway has been shown to be essential for craniofacial development. Although mandibular arch derivatives are largely absent in Shh null mice, little is known about the role of Hh signaling during Meckel's cartilage development per se. Mandible development is dependent on the morphogenesis of Meckel's cartilage, which then serves as a template for subsequent skeletal differentiation. In this study, we examine the biological function of Hh signaling during Meckel's cartilage development in vivo and in vitro. E13.5 Shh null mice present a small mesenchymal condensation in the region of a presumptive Meckel's cartilage in the hypoplastic mandibular arch. By E15.5, the Shh mutant exhibits a mere remnant of the mandibular arch, without evidence of Meckel's cartilage differentiation. Further, wild-type embryonic (E11 or E12) mandibular explants cultured for up to 5 days in the presence of cyclopamine, a steroidal alkaloid that specifically disrupts the Hh signaling pathway, exhibit a stage-dependent inhibition of Meckel's cartilage chondroblast differentiation to mature chondrocytes. This phenotype can be rescued by exogenous FGF8, a downstream effector of Hh signaling. Taken together, our results indicate that the Hh signaling pathway is critical to Meckel's cartilage ontogenesis and the rate of chondrogenesis, but not to initial primordium formation. The reliance on Hh signaling is stage dependent. Copyright (C) 2005 S. Karger AG, Basel.
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