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Six2 regulates palate development by inhibiting palatal bone formation during development
Abstract   Open access   Peer reviewed

Six2 regulates palate development by inhibiting palatal bone formation during development

Yan Yan Sweat, Mason Sweat, Maurisa Mansaray, Irfan Saadi, Salil Lachke, Azeez Butali and Brad Amendt
The FASEB journal, Vol.32(S1), pp.15.1-15.1
04/2018
DOI: 10.1096/fasebj.2018.32.1_supplement.15.1
url
https://doi.org/10.1096/fasebj.2018.32.1_supplement.15.1View
Published (Version of record) Open Access

Abstract

Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial defect, with a frequency of 1 in 500 to 1 in 2500 live births depending on the population, and lifelong care can cost more than $100,000. In mice, secondary palate development occurs from E11.5 to E17.5, and consists of outgrowth, elevation, extension and fusion processes. At any stage during palatogenesis, the disruption of these processes could cause cleft palate, and these processes are all regulated in part by palatal mesenchyme. Objective To examine Six2, a transcription factor previously shown to play a role in craniofacial and kidney development, for a role in clefting predicted by the SYSFACE tool. Methods Six2 knockout mice were generated and examined for clefting at different embryonic stages and P0 and craniofacial developmental defects. Results We demonstrate that ablation of Six2 contributes to palatogenesis. We have characterized the clefting phenotype in Six2−/− embryos, demonstrating that the palate shelves fail to extend to the midline and contain premature ossified tissue compared to wild‐type (WT) littermates. The expression of Runx2 and its target Osx were higher in Six2−/− palates and surrounding maxilla with cleft than in control littermates. Histochemistry and immunohistochemistry experiments demonstrate premature ossification by specific cells in the Six2−/− palate. Conclusions Six2 is a regulator of palate development and it acts by negatively regulating the ossification of palatal mesenchyme. In Six2−/− mice, ectopic ossification prevents the extension of the palate shelves causing cleft. Support or Funding Information The University of Iowa, College of Dentistry This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.

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