title: Shh, Fgf4 and Hoxd gene expression in the mouse limb mutant hypodactyly.
abstract: The semidominant mouse mutation hypodactyly (Hd), caused by a deletion within the Hoxa13 gene, results in reduced digits; heterozygotes lack digit I in the hindlimb and homozygotes have only one digit on each limb. We investigated expression of Shh and Fgf4 signaling molecules involved in digit specification in mutant limb buds. Shh and Fgf4 are expressed in the posterior part of the limb buds as normal but expression may be slightly prolonged. The extent of digit reduction in hypodactyly is much more severe than in the Hoxa13 deficient mouse and resembles that in the Hoxa13(-/-)/Hoxd13(-/-) double mutant mouse. We found that the pattern of Hoxd13 and Hoxd11 transcripts was not markedly different in the mutant compared with the normal limbs even though the mutant limbs are narrower. Therefore Hoxd genes are transcribed as normal in the mutant. This makes it likely that the severe digit reductions in hypodactyly are caused by interference with Hoxd13 function at the protein level. Similar interactions between mutant and normal HOX gene products have been suggested to occur in the human semidominant disorder, synpolydactyly, caused by mutations in HOXD13.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Robertson
authors.forename: C
authors.initials: C
authors.lastname: Tickle
authors.forename: S M
authors.initials: SM
authors.lastname: Darling
mesh_terms: D000818:Animals; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics*; D017403:In Situ Hybridization; D018878:Limb Buds / Q000196:embryology / Q000378:metabolism*; D017880:Limb Deformities, Congenital / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009154:Mutation; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
chemical_list: C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C490939:Hoxd11 protein, mouse; C084118:Hoxd13 protein, mouse; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C099959:homeobox protein HOXA13; D005346:Fibroblast Growth Factors