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En1 and Wnt7a interact with Dkk1 during limb development in the mouse
- Source :
- Developmental Biology. August 1, 2004, Vol. 272 Issue 1, p134, 11 p.
- Publication Year :
- 2004
-
Abstract
- Wnt signaling plays an essential role in induction and development of the limb. Missing digits are one consequence of the reduced Wnt signaling in Wnt7a null mice, while extra digits result from excess Wnt signaling in mice null for the Wnt antagonist Dkk1. The extra digits and expanded apical ectodermal ridge (AER) of Dkk1-deficient mice closely resemble En1 null mice. To evaluate the in vivo interaction between En1 and the canonical Wnt signaling pathway, we generated double and triple mutants combining the hypomorphic doubleridge allele of Dkk1 with null alleles of En1 and Wnt7a. Reducing Dkk1 expression in [Dkk1.sup.d/+] [Wnt7a.sup.-/-] double mutants prevented digit loss, indicating that Wnt7a acts through the canonical pathway during limb development. Reducing Dkk1 levels in [Dkk1.sup.d/d][En1.sup.-/-] double mutants resulted in severe phenotypes not seen in either single mutant, including fused bones in the autopod, extensive defects of the zeugopod, and loss of the ischial bone. The subsequent elimination of Wnt7a in [Dkk1.sup.d/d][En1.sup.-/-][Wnt7a.sup.-/-] triple mutants resulted in correction of most, but not all, of these defects. The failure of Wnt7a inactivation to completely correct the limb defects of [Dkk1.sup.d/d][En1.sup.-/-] double mutants indicates that Wnt7a is not the only gene regulated by En1 during development of the mouse limb. Keywords: Limb development; Wnt signaling; AER; Dkk1; En1; Wnt7a
- Subjects :
- Developmental biology -- Research
Biological sciences
Subjects
Details
- Language :
- English
- ISSN :
- 00121606
- Volume :
- 272
- Issue :
- 1
- Database :
- Gale General OneFile
- Journal :
- Developmental Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.119850392