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TGFβR3 is required for normal vascularization and ossification of the palate (342.5)
Author(s) -
Hill Cynthia,
Barnett Joey,
Goudy Steven
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.342.5
Subject(s) - osteoblast , transforming growth factor , ossification , biology , microbiology and biotechnology , morphogenesis , receptor , bone morphogenetic protein , anatomy , medicine , endocrinology , genetics , gene , in vitro
Cleft palate occurs in up to 1:500 live births associated with mutations in multiple genes. Palatogenesis involves a complex choreography of palate shelf elongation, elevation, and fusion. Transforming Growth Factor β (TGFβ) and Bone Morphogenic Protein 2 (BMP2) are known regulators of palatal development, but the contributions of the specific receptors remain elusive. The Type III TGFβ Receptor (TGFβR3) binds all three TGFβ ligands, inhibin, and BMP2. To address the role of TGFβR3 during palatal development we examined Tgfbr3 ‐/‐ mice. These mice do not survive to E15.5 when palate fusion occurs, but at E14.5, palatal elongation and elevation had failed. Tgfbr3 ‐/‐ embryos display unorganized and reduced vascularization of the palate at E13.5 and E14.5 which was accompanied by aberrant expression of arterial, venous, and lymphatic markers. Analysis of osteoblast differentiation demonstrated reduced expression of osteoblast determinants at E13.5 and E14.5. In vitro bone mineralization assays revealed reduced capacity of Tgfbr3 ‐/‐ mouse embryonic palatal mesenchymal cells to undergo osteoblast differentiation and to form bone which was rescued by overexpression of TGFβR3. These data demonstrate that TGFβR3 contributes to palatal development by regulating vascularization and osteoblast differentiation. Grant Funding Source : 5K08DE17953‐5