Survival of Hoxa13 homozygous mutants reveals a novel role in digit patterning and appendicular skeletal development

Authors

  • Wilma D. Perez,

    1. Shriners Hospital for Children Research Department, Portland, Oregon
    2. Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon
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  • Crystal R. Weller,

    1. College of Veterinary Medicine, Oregon State University, Corvallis, Oregon
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  • Siming Shou,

    1. University of Chicago Microarray Core, Chicago, Illinois
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  • H. Scott Stadler

    Corresponding author
    1. Shriners Hospital for Children Research Department, Portland, Oregon
    2. Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon
    • Shriners Hospital for Children Research Department, 3101 SW Sam Jackson Park Road, Portland, OR 97239
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Abstract

The loss of HOXA13 function severely disrupts embryonic limb development. However, because embryos lacking HOXA13 die by mid-gestation, the defects present in the mutant limb could arise as a secondary consequence of failing embryonic health. In our analysis of the mutant Hoxa13GFP allele, we identified a surviving cohort of homozygous mutants exhibiting severe limb defects including: missing phalanx elements, fusions of the carpal/tarsal elements, and significant reductions in metacarpal/metatarsal length. Characterization of prochondrogenic genes in the affected carpal/tarsal regions revealed significant reduction in Gdf5 expression, whereas Bmp2 expression was significantly elevated. Analysis of Gdf5 mRNA localization also revealed diffuse expression in the carpal/tarsal anlagen, suggesting a role for HOXA13 in the organization of the cells necessary to delineate individual carpal/tarsal elements. Together these results identify Gdf5 as a potential target gene of HOXA13 target gene and confirm a specific role for HOXA13 during appendicular skeletal development. Developmental Dynamics 239:446–457, 2010. © 2009 Wiley-Liss, Inc.

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