Syndactyly of Ft/+ mice correlates with an imbalance in bmp4 and fgf8 expression.
The most obvious phenotype of Ft/+ mice is a syndactyly of fore limbs characterised by a fusion of the tips of digits 1 to 4. The tempospatial expression of genes involved in limb development revealed that patterning of Ft/+ limb buds is not affected by the mutation. However, an upregulation of Bmp4 in the anterior-distal region of the limb bud at d12.0 of embryonic development is accompanied by a loss of Fgf8 expression in the distal part of the AER. Downstream target genes of Bmp action such as Msx1 and 2 are upregulated. This induction of the signalling cascade indicates ectopic expression of functional Bmp4. Nevertheless, analysis of physical parameters of bones from adult mice revealed a reduction of the bone mass of the autopod. The data suggest a negative effect of Bmp4 on Fgf8 expression and a positive influence on the induction of bone elements.
Heymer
J
J
Institut für Molekularbiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Rüther
U
U
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D005121:Extremities / Q000033:anatomy & histology / Q000196:embryology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D018878:Limb Buds / Q000378:metabolism; D051957:MSX1 Transcription Factor; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D009929:Organ Size / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013576:Syndactyly / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D051957:MSX1 Transcription Factor; D015513:Oncogene Proteins; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C496457:Fgf8 protein, mouse; C000618551:Gli2 protein, mouse; C084119:MSX2 protein