The D1x5 and D1x6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development

被引:318
作者
Robledo, RF [1 ]
Rajan, L [1 ]
Li, X [1 ]
Lufkin, T [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Brookdale Ctr Dev & Mol Biol, New York, NY 10029 USA
关键词
embryo; mouse; transgenic; knockout; cartilage; limb;
D O I
10.1101/gad.988402
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll) gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In Drosophila, Dll is expressed in the distal portion of the developing appendages and is critical for the development of distal structures. In addition, human Dlx5 and Dlx6 homeobox genes have been identified as possible candidate genes for the autosomal dominant form of the split-hand/split-foot malformation (SHFM), a heterogeneous limb disorder characterized by missing central digits and claw-like distal extremities. Targeted inactivation of Dlx5 and Dlx6 genes in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities, leading to perinatal lethality. For the first time, Dlx/Dll gene products are shown to be critical regulators of mammalian limb development, as combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue D/x/Dll function in limb outgrowth.
引用
收藏
页码:1089 / 1101
页数:13
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