Defining a critical period in calvarial development for Hedgehog pathway antagonist-induced frontal bone dysplasia in mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-03

AUTHORS

Yuanjing Jiang, Shixian Zhang, Chuanqing Mao, Yongzhen Lai, Di Wu, Hu Zhao, Caiyu Liao, Weihui Chen

ABSTRACT

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg-1 or 150 mg•kg-1 body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg-1. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death. More... »

PAGES

3

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41368-018-0040-z

DOI

http://dx.doi.org/10.1038/s41368-018-0040-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111061180

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30783111


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RDF/XML is a standard XML format for linked data.

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This table displays all metadata directly associated to this object as RDF triples.

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