title: Doubleridge, a mouse mutant with defective compaction of the apical ectodermal ridge and normal dorsal-ventral patterning of the limb.
abstract: doubleridge is a transgene-induced mutation characterized by polydactyly and syndactyly of the forelimbs. The transgene insertion maps to the proximal region of chromosome 19. During embryonic development of the mutant forelimb, delayed elevation and compaction of the apical ectodermal ridge (AER) produces a ridge that is abnormally broad and flat. Fgf8 expression persists in the ventral forelimb ectoderm of the mutant until E10.5. Strong expression of Fgf8 and other markers at the borders of the AER at E11.5 gives the appearance of a double ridge. At E11.5, apoptotic cells are distributed across the broadened ridge, but at E13.5, there is reduced apoptosis in the interdigital regions. The Shh expression domain is widely spaced at the posterior margin of the AER. The doubleridge AER is morphologically similar to that of En1 null mice, but the expression of En1 and Wnt7a is properly restricted in doubleridge, and the dorsal and ventral structures are correctly determined. doubleridge thus exhibits an unusual limb phenotype combining abnormal compaction of the AER with normal dorsal/ventral patterning.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-0618, USA.
authors.forename: Maja
authors.initials: M
authors.lastname: Adamska
authors.forename: Bryan T
authors.initials: BT
authors.lastname: MacDonald
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Meisler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D002874:Chromosome Mapping; D004475:Ectoderm / Q000166:cytology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics; D005552:Forelimb / Q000002:abnormalities* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D017689:Polydactyly / Q000196:embryology / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D013576:Syndactyly / Q000196:embryology / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D051153:Wnt Proteins
chemical_list: C080330:En1 protein, mouse; C496457:Fgf8 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors