title: Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins.
abstract: Mechanisms that regulate the size and shape of bony structures are largely unknown. The molecular identification of the fin length mutant short fin (sof), which causes defects in the length of bony fin ray segments, may provide insights regarding the regulation of bone growth. In this report, we demonstrate that the sof phenotype is caused by mutations in the connexin43 (cx43) gene. This conclusion is supported by genetic mapping, reduced expression of cx43 in the original sof allele (sofb123), identification of missense mutations in three ENU-induced alleles, and by demonstration of partially abrogated cx43 function in sofb123 embryos. Expression of cx43 was identified in cells flanking the germinal region of newly growing segments as well as in the osteoblasts at segment boundaries. This pattern of cx43 expression in cells lateral to new segment growth is consistent with a model where cx43-expressing cells represent a biological ruler that measures segment size. This report identifies the first gene identification for a fin length mutation (sof) as well as the first connexin mutations in zebrafish, and therefore reveals a critical role for local cell-cell communication in the regulation of bone size and growth.
authors.affiliation: Lehigh University, 111 Research Drive, Iacocca B-217, Bethlehem, PA 18015, USA. mki3@lehigh.edu
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Iovine
authors.forename: Emmett P
authors.initials: EP
authors.lastname: Higgins
authors.forename: Anna
authors.initials: A
authors.lastname: Hindes
authors.forename: Brian
authors.initials: B
authors.lastname: Coblitz
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Johnson
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000235:genetics*; D001861:Bone Regeneration / Q000235:genetics; D002874:Chromosome Mapping; D018031:Connexin 43 / Q000235:genetics* / Q000502:physiology; D004247:DNA / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D018031:Connexin 43; D029961:Zebrafish Proteins; D004247:DNA