Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1-null mice

被引:63
作者
Han, Jun [1 ]
Mayo, Julie [1 ]
Xu, Xun [1 ]
Li, Jingyuan [1 ]
Bringas, Pablo, Jr. [1 ]
Maas, Richard L. [2 ,3 ]
Rubenstein, John L. R. [4 ]
Chai, Yang [1 ]
机构
[1] Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA
[2] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA
来源
DEVELOPMENT | 2009年 / 136卷 / 24期
关键词
Msx1; Dlx5; Cranial neural crest (CNC) cells; Palate; Shh; CRANIAL NEURAL CREST; SELECTIVE TOOTH AGENESIS; BRANCHIAL ARCHES; GROWTH-FACTOR; MSX1; MORPHOGENESIS; GENES; EXPRESSION; MUTATION; BMP;
D O I
10.1242/dev.036723
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cleft palate represents one of the most common congenital birth defects in human. During embryonic development, palatal shelves display oronasal (O-N) and anteroposterior polarity before the onset of fusion, but how the O-N pattern is established and how it relates to the expansion and fusion of the palatal shelves are unknown. Here we address these questions and show that O-N patterning is associated with the expansion and fusion of the palatal shelves and that Dlx5 is required for the O-N patterning of palatal mesenchyme. Loss of Dlx5 results in downregulation of Fgf7 and expanded Shh expression from the oral to the nasal side of the palatal shelf. This expanded Shh signaling is sufficient to restore palatal expansion and fusion in mice with compromised palatal mesenchymal cell proliferation, such as Msx1-null mutants. Exogenous Fgf7 inhibits Shh signaling and reverses the cranial neural crest (CNC) cell proliferation rescue in the Msx1/Dlx5 double knockout palatal mesenchyme. Thus, Dlx5-regulated Fgf7 signaling inhibits the expression of Shh, which in turn controls the fate of CNC cells through tissue-tissue interaction and plays a crucial role during palatogenesis. Our study shows that modulation of Shh signaling may be useful as a potential therapeutic approach for rescuing cleft palate.
引用
收藏
页码:4225 / 4233
页数:9
相关论文
共 43 条
[1]  
Bei M, 2000, DEVELOPMENT, V127, P4711
[2]  
Bellusci S, 1997, DEVELOPMENT, V124, P4867
[3]   Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation:: Mirror of the past? [J].
Beverdam, A ;
Merlo, GR ;
Paleari, L ;
Mantero, S ;
Genova, F ;
Barbieri, O ;
Janvier, P ;
Levi, G .
GENESIS, 2002, 34 (04) :221-227
[4]   Recent advances in craniofacial morphogenesis [J].
Chai, Yang ;
Maxson, Robert E., Jr. .
DEVELOPMENTAL DYNAMICS, 2006, 235 (09) :2353-2375
[5]   Sonic hedgehog signalling inhibits palatogenesis and arrests tooth development in a mouse model of the nevoid basal cell carcinoma syndrome [J].
Cobourne, Martyn T. ;
Xavier, Guilherme M. ;
Depew, Michael ;
Hagan, Louise ;
Sealby, Jane ;
Webster, Zoe ;
Sharpe, Paul T. .
DEVELOPMENTAL BIOLOGY, 2009, 331 (01) :38-49
[6]   Restriction of sonic hedgehog signalling during early tooth development [J].
Cobourne, MT ;
Miletich, I ;
Sharpe, PT .
DEVELOPMENT, 2004, 131 (12) :2875-2885
[7]   Specification of jaw subdivisions by Dix genes [J].
Depew, MJ ;
Lufkin, T ;
Rubenstein, JLR .
SCIENCE, 2002, 298 (5592) :381-385
[8]  
Depew MJ, 1999, DEVELOPMENT, V126, P3831
[9]  
FERGUSON MWJ, 1988, DEVELOPMENT, V103, P41
[10]   Keratinocyte growth factor is required for hair development but not for wound healing [J].
Guo, LF ;
Degenstein, L ;
Fuchs, E .
GENES & DEVELOPMENT, 1996, 10 (02) :165-175