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

First Author  Perez WD Year  2010
Journal  Dev Dyn Volume  239
Issue  2 Pages  446-57
PubMed ID  20034107 Mgi Jnum  J:156949
Mgi Id  MGI:4422128 Doi  10.1002/dvdy.22183
Citation  Perez WD, et al. (2010) Survival of Hoxa13 homozygous mutants reveals a novel role in digit patterning and appendicular skeletal development. Dev Dyn 239(2):446-57
abstractText  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 Hoxa13(GFP) 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.
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