Paired-related homeobox genes cooperate in handplate and hindlimb zeugopod morphogenesis

被引:51
作者
Lu, MF
Cheng, HT
Lacy, AR
Kern, MJ
Argao, EA
Potter, SS
Olson, EN
Martin, JF [1 ]
机构
[1] Texas A&M Univ, Alkek Inst Biosci & Technol, Ctr Canc Biol & Nutr, Dept Med Biochem & Genet, Houston, TX 77030 USA
[2] Univ Texas, SW Med Ctr, Hamon Ctr Basic Canc Res, Dept Mol Biol & Oncol, Dallas, TX 75235 USA
[3] Childrens Hosp Res Fdn, Div Basic Sci Res, Cincinnati, OH 45229 USA
[4] Med Univ S Carolina, Dept Anat & Cell Biol, Charleston, SC 29425 USA
[5] Univ Arkansas Med Sci Hosp, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA
关键词
morphogenesis; limb development; gene targeting; paired homeobox;
D O I
10.1006/dbio.1998.9116
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The closely related homeobox genes prx-1 and prx-2 are expressed in lateral plate and limb bud mesoderm, but targeted inactivation of these genes failed to demonstrate a limb phenotype. Here we report that mice carrying compound mutations in prx-1 and prx-2 have severe limb deformities. In the forelimb autopod, pre- and postaxial polydactyly were found most commonly, but also syndactyly, oligodactyly, and abnormal digit placement affecting posterior elements were observed. In the hindlimb, preaxial polydactyly with variable expressivity was seen in all cases. Extreme distal digit duplications were seen in both the fore- and hindlimbs. prx-1; prx-2 double-mutant mice also displayed extreme shortening and impaired ossification of the hindlimb zeugopods. Integrity of the forelimb apical ectodermal ridge was abnormal as determined by expression of FGF8 and BMP4. Expression of msx-1 and msx-2, markers for BMP signaling pathways, was absent in regions of the posterior handplates, while expression of Shh and patched was unaffected. The mutant phenotypes were dosage dependent, since prx-1 -/-; prx-2 +/- mice also displayed severe limb abnormalities. These data suggest that prx-1 and prx-2 cooperatively regulate handplate and hindlimb zeugopod morphogenesis through BMP-mediated signaling pathways. (C) 1999 Academic Press.
引用
收藏
页码:145 / 157
页数:13
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