Type III transforming growth factor beta receptor regulates vascular and osteoblast development during palatogenesis. Issue 2 (1st December 2014)

• Record Type: Journal Article
• Authors: Hill, Cynthia R.; Jacobs, Britni H.; Brown, Christopher B.; Barnett, Joey V.; Goudy, Steven L.
• Is Part Of: Developmental dynamics. Volume 244:Issue 2(2015:Feb.)
• Page Start: 122
• Page End: 133
• Publication Date: 2014-12-01
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24225
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dvdy24225-sec-0001" sec-type="section"> <p> <bold> <underline>Background:</underline> </bold> Cleft palate occurs in up to 1:1, 000 live births and is associated with mutations in multiple genes. Palatogenesis involves a complex choreography of palatal shelf elongation, elevation, and fusion. Transforming growth factor β (TGFβ) and bone morphogenetic protein 2 (BMP2) canonical signaling is required during each stage of palate development. The type III TGFβ receptor (TGFβR3) binds all three TGFβ ligands and BMP2, but its contribution to palatogenesis is unknown. <bold><underline>Results:</underline></bold> The role of TGFβR3 during palate formation was found to be during palatal shelf elongation and elevation. <italic>Tgfbr3<sup>−</sup><sup>/</sup><sup>−</sup></italic> embryos displayed reduced palatal shelf width and height, changes in proliferation and apoptosis, and reduced vascular and osteoblast differentiation. Abnormal vascular plexus organization as well as aberrant expression of arterial (<italic>Notch1</italic>, <italic>Alk1</italic>), venous (<italic>EphB4</italic>), and lymphatic (<italic>Lyve1</italic>) markers was also observed. Decreased osteoblast differentiation factors (<italic>Runx2</italic>, <italic>alk phos</italic>, <italic>osteocalcin</italic>, <italic>col1A1</italic>, and <italic>col1A2</italic>) demonstrated poor mesenchymal cell commitment to the osteoblast lineage within the maxilla and palatal shelves in <italic>Tgfbr3<sup>−</sup><sup>/</sup><sup>−</sup></italic> embryos. Additionally, in vitro bone mineralization induced by osteogenic medium (OM+BMP2) was insufficient in <italic>Tgfbr3<sup>−</sup><sup>/</sup><sup>−</sup></italic> palatal mesenchyme, but mineralization was rescued by overexpression of TGFβR3. <bold><underline>Conclusions:</underline></bold> These data reveal a critical, previously unrecognized role for TGFβR3 in vascular and osteoblast development during palatogenesis. <italic>Developmental Dynamics, 2014</italic>. © 2014 Wiley Periodicals, Inc. <italic>Developmental Dynamics 244:122–133, 2015</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>