| First Author | Hill CR | Year | 2015 |
| Journal | Dev Dyn | Volume | 244 |
| Issue | 2 | Pages | 122-33 |
| PubMed ID | 25382630 | Mgi Jnum | J:218259 |
| Mgi Id | MGI:5617089 | Doi | 10.1002/dvdy.24225 |
| Citation | Hill CR, et al. (2015) Type III transforming growth factor beta receptor regulates vascular and osteoblast development during palatogenesis. Dev Dyn 244(2):122-33 |
| abstractText | BACKGROUND: 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 beta (TGFbeta) and bone morphogenetic protein 2 (BMP2) canonical signaling is required during each stage of palate development. The type III TGFbeta receptor (TGFbetaR3) binds all three TGFbeta ligands and BMP2, but its contribution to palatogenesis is unknown. RESULTS: The role of TGFbetaR3 during palate formation was found to be during palatal shelf elongation and elevation. Tgfbr3(-) (/) (-) 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 (Notch1, Alk1), venous (EphB4), and lymphatic (Lyve1) markers was also observed. Decreased osteoblast differentiation factors (Runx2, alk phos, osteocalcin, col1A1, and col1A2) demonstrated poor mesenchymal cell commitment to the osteoblast lineage within the maxilla and palatal shelves in Tgfbr3(-) (/) (-) embryos. Additionally, in vitro bone mineralization induced by osteogenic medium (OM+BMP2) was insufficient in Tgfbr3(-) (/) (-) palatal mesenchyme, but mineralization was rescued by overexpression of TGFbetaR3. CONCLUSIONS: These data reveal a critical, previously unrecognized role for TGFbetaR3 in vascular and osteoblast development during palatogenesis. Developmental Dynamics, 2014. (c) 2014 Wiley Periodicals, Inc. Developmental Dynamics 244:122-133, 2015. (c) 2014 Wiley Periodicals, Inc. |
