| First Author | Huang H | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 13 | Pages | 7107-18 |
| PubMed ID | 26826126 | Mgi Jnum | J:232434 |
| Mgi Id | MGI:5779245 | Doi | 10.1074/jbc.M115.690875 |
| Citation | Huang H, et al. (2016) Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence. J Biol Chem 291(13):7107-18 |
| abstractText | Mouse gene inactivation has shown that the transcription factorSox11is required for mouse palatogenesis. However, whetherSox11is primarily involved in the regulation of palatogenesis still remains elusive. In this study, we explored the role ofSox11in palatogenesis by analyzing the developmental mechanism in cleft palate formation in mutants deficient inSox11. Sox11is expressed both in the developing palatal shelf and in the surrounding structures, including the mandible. We found that cleft palate occurs only in the mutant in whichSox11is directly deleted. As in the wild type, the palatal shelves in theSox11mutant undergo outgrowth in a downward direction and exhibit potential for fusion and elevation. However, mutant palatal shelves encounter clefting, which is associated with a malpositioned tongue that results in physical obstruction of palatal shelf elevation at embryonic day 14.5 (E14.5). We found that loss ofSox11led to reduced cell proliferation in the developing mandibular mesenchyme via Cyclin D1, leading to mandibular hypoplasia, which blocks tongue descent. Extensive analyses of gene expression inSox11deficiency identified FGF9 as a potential candidate target ofSox11in the modulation of cell proliferation both in the mandible and the palatal shelf between E12.5 and E13.5. Finally we show, usingin vitroassays, thatSox11directly regulates the expression ofFgf9and that application of FGF9 protein toSox11-deficient palatal shelves restores the rate of BrdU incorporation. Taken together, the palate defects presented in theSox11loss mutant mimic the clefting in the Pierre Robin sequence in humans. |
