title: Zebrafish tbx5 paralogs demonstrate independent essential requirements in cardiac and pectoral fin development.
abstract: BACKGROUND
  T-box genes constitute a large family of transcriptional regulators involved in developmental patterning. Homozygous mutation of tbx5 leads to embryonic lethal cardiac phenotypes and forelimb malformations in vertebrate models. Haploinsufficiency of tbx5 results in Holt-Oram syndrome, a human congenital disease characterized by cardiac and forelimb defects. Homozygous mutation of zebrafish tbx5a leads to lethal defects in cardiac looping morphogenesis, blocks pectoral fin initiation, and impairs outgrowth. Recently, a second zebrafish tbx5 gene was described, termed tbx5b.
  
  
  RESULTS
  Our phylogenetic analyses confirm tbx5b as a paralog that likely arose in the teleost-specific whole genome duplication ∼270 MYA. Using morpholino depletion studies, we find that tbx5b is required in the heart for embryonic survival, and influences the timing and morphogenesis of pectoral fin development. Because tbx5a hypomorphic mutations are embryonic lethal, tbx5a and tbx5b functions in the heart must not be completely redundant. Consistent with this hypothesis, simultaneous depletion of both tbx5 paralogs did not lead to more severe phenotypes, and injection of wild-type mRNA from one tbx5 paralog was not sufficient to cross-rescue phenotypes of the paralogous gene.
  
  
  CONCLUSIONS
  Collectively, these data indicate that, despite similar spatio-temporal expression patterns, tbx5a and tbx5b have independent functions in heart and fin development.
authors: Colorado State University CSU, Department of Biology, Fort Collins, Colorado 80523, USA.
authors: Lindsay E
authors: LE
authors: Parrie
authors: Erin M
authors: EM
authors: Renfrew
authors: Aimee Vander
authors: AV
authors: Wal
authors: Rachel Lockridge
authors: RL
authors: Mueller
authors: Deborah M
authors: DM
authors: Garrity
mesh_terms: D000595:Amino Acid Sequence; D058500:Animal Fins / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D004625:Embryo, Nonmammalian; D020440:Gene Duplication; D018507:Gene Expression Regulation, Developmental; D049810:Genetic Speciation; D016678:Genome / Q000235:genetics; D006321:Heart / Q000196:embryology*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics; D017385:Sequence Homology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5