Shox2-deficient mice exhibit a rare type of incomplete clefting of the secondary palate
Author:
Yu Ling1, Gu Shuping1, Alappat Sylvia1, Song Yiqiang1, Yan Mingquan1, Zhang Xiaoyun1, Zhang Guozhong2, Jiang Yiping1, Zhang Zunyi1, Zhang Yanding2, Chen YiPing12
Affiliation:
1. Division of Developmental Biology, Department of Cell and Molecular Biology,and Center for Bioenvironmental Research, Tulane University, New Orleans, LA 70118, USA 2. College of Bioengineering, Fujian Normal University, Fuzhou, Fujian 350007, PR China
Abstract
The short stature homeobox gene SHOX is associated with idiopathic short stature in humans, as seen in Turner syndrome and Leri-Weill dyschondrosteosis, while little is known about its close relative SHOX2. We report the restricted expression of Shox2 in the anterior domain of the secondary palate in mice and humans. Shox2-/- mice develop an incomplete cleft that is confined to the anterior region of the palate, an extremely rare type of clefting in humans. The Shox2-/- palatal shelves initiate, grow and elevate normally, but the anterior region fails to contact and fuse at the midline, owing to altered cell proliferation and apoptosis, leading to incomplete clefting within the presumptive hard palate. Accompanied with these cellular alterations is an ectopic expression of Fgf10 and Fgfr2c in the anterior palatal mesenchyme of the mutants. Tissue recombination and bead implantation experiments revealed that signals from the anterior palatal epithelium are responsible for the restricted mesenchymal Shox2 expression. BMP activity is necessary but not sufficient for the induction of palatal Shox2 expression. Our results demonstrate an intrinsic requirement for Shox2 in palatogenesis, and support the idea that palatogenesis is differentially regulated along the anteroposterior axis. Furthermore, our results demonstrate that fusion of the posterior palate can occur independently of fusion in the anterior palate.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference55 articles.
1. Alappat, S. R., Zhang, Z., Suzuki, K., Zhang, X., Liu, H.,Jiang, R., Yamada, G. and Chen, Y. P. (2005). The cellular and molecular etiology of the cleft secondary palate in Fgf10 mutant mice. Dev. Biol.277,102-113. 2. Allanson, J. E., Hennekam, R. C. and Ireland, M.(1997). De Lange syndrome: subjective and objective comparison of the classical and mild phenotypes. J. Med. Genet.34,645-650. 3. Aqua, M. S., Rizzu, P., Lindsay, E. A., Shaffer, L. G., Zackai,E. H., Overhauser, J. and Baldini, A. (1995). Duplication 3q syndrome: molecular delineation of the critical region. Am. J. Med. Genet.55,33-37. 4. Baldwin, C. T., Hoth, C. F., Amos, J. A., da-Silva, E. O. and Milunsky, A. (1992). An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature355,637-638. 5. Barlow, A. J. and Francis-West, P. H. (1997). Ectopic application of BMP-2 and BMP-4 can change patterning of developing chick facial primordia. Development124,391-398.
Cited by
132 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|