@ARTICLE{TreeBASE2Ref20627, author = {Lindsay E Parrie and Erin M Renfrew and Rachel Lockridge Mueller and Deborah M Garrity}, title = {Zebrafish tbx5 paralogs are not functionally redundant in cardiac or pectoral fin development}, year = {2012}, keywords = {zebrafish, cardiac, T-box, embryonic, redundancy, fin}, doi = {}, url = {http://}, pmid = {}, journal = {Developmental Biology}, volume = {}, number = {}, pages = {}, abstract = {T-box genes constitute a large family of transcriptional regulators involved in developmental patterning processes. Homozygous mutation of the T-box transcription factor tbx5 leads to embryonic lethal cardiac phenotypes and forelimb malformations in vertebrate models. Haploinsufficiency of Tbx5 results in Holt-Oram Syndrome (HOS), a human congenital disease characterized by cardiac and forelimb defects. Homozygous mutation of zebrafish tbx5a also leads to lethal defects in cardiac looping morphogenesis and adversely affects pectoral fin initiation and outgrowth. Recently, a second zebrafish tbx5 paralog was described, termed tbx5b. Our phylogenetic analyses show that tbx5a and tbx5b in zebrafish likely result from the teleost-specific whole genome duplication event ~270 million years ago. Since tbx5a loss of function mutations are embryonic lethal, the functions of tbx5a and tbx5b in the heart must not be completely redundant. However, the extent of their functional divergence remains uncharacterized. We show here, via morpholino depletion studies, that tbx5b is required in the embryonic heart, and that the phenotypes are similar, but not identical, to those of homozygous tbx5a mutants. In addition, tbx5b depletion leads to defects in the timing and morphogenesis of pectoral fin development. Simultaneous depletion of both tbx5 paralogs does not lead to more severe phenotypes, and injection of wild-type mRNA from one tbx5 paralog is not sufficient to cross-rescue the phenotypes of the paralogous gene. Collectively, these data indicate that, in the heart, both tbx5a and tbx5b have essential, independently required functions. In the fin, tbx5a alone is required for fin bud initiation, but both genes are independently required for patterning and morphogenesis. Therefore, this work demonstrates a functional divergence between the two zebrafish tbx5 paralogs since their origin ~270 million years ago, although the spatio-temporal expression patterns of the paralogs are very similar.} }

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