title: Impairment of Sox9 expression in limb buds of rats homozygous for hypodactyly mutation.
abstract: Rat hypodactyly (hd) is an autosomal recessive mutation manifesting in homozygotes as reduction or loss of digits II and III. We mapped the hd allele to a short segment of chromosome 10, containing 16 genes. None of these genes has been shown to influence limb development yet. In situ hybridization showed no changes in several important patterning genes (Shh, Fgf8, Bmp2, 4, 7). However, we found that expression of cartilage condensation marker Sox9, and Bmp receptor Bmpr1b (acting as an upstream activator of Sox9 expression) is absent from the subepithelial mesenchyme of the digit condensations II and III. The failure of the chondrogenic condensations to extend towards the subepithelial mesenchyme may reduce the size of digit primordia and underlie the subsequent loss of phalanges and reduction of metacarpals/metatarsals in hd rats.
authors.affiliation: Charles University in Prague, First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic. frantisek.liska@lf1.cuni.cz
authors.forename: F
authors.initials: F
authors.lastname: Liska
authors.forename: P
authors.initials: P
authors.lastname: Snajdr
authors.forename: S
authors.initials: S
authors.lastname: Stricker
authors.forename: C
authors.initials: C
authors.lastname: Gosele
authors.forename: D
authors.initials: D
authors.lastname: Krenová
authors.forename: S
authors.initials: S
authors.lastname: Mundlos
authors.forename: N
authors.initials: N
authors.lastname: Hubner
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000378:metabolism; D005121:Extremities; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D018878:Limb Buds / Q000002:abnormalities* / Q000378:metabolism*; D008297:Male; D009154:Mutation; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D055758:SOX9 Transcription Factor; C099959:homeobox protein HOXA13; C498216:Bmpr1b protein, rat; D052005:Bone Morphogenetic Protein Receptors, Type I