title: Survival of Hoxa13 homozygous mutants reveals a novel role in digit patterning and appendicular skeletal development.
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 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.
authors.affiliation: Shriners Hospital for Children Research Department, Portland, Oregon, USA.
authors.forename: Wilma D
authors.initials: WD
authors.lastname: Perez
authors.forename: Crystal R
authors.initials: CR
authors.lastname: Weller
authors.forename: Siming
authors.initials: S
authors.lastname: Shou
authors.forename: H Scott
authors.initials: HS
authors.lastname: Stadler
mesh_terms: D000818:Animals; D016923:Cell Death; D049109:Cell Proliferation; D005260:Female; D005529:Foot Bones / Q000196:embryology*; D055428:Growth Differentiation Factor 5 / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D055758:SOX9 Transcription Factor / Q000378:metabolism; D012863:Skeleton
chemical_list: C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D018398:Homeodomain Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C099959:homeobox protein HOXA13