Distinct tissue-specific requirements for the zebrafish tbx5 genes during heart, retina and pectoral fin development.
The transcription factor Tbx5 is expressed in the developing heart, eyes and anterior appendages. Mutations in human TBX5 cause Holt-Oram syndrome, a condition characterized by heart and upper limb malformations. Tbx5-knockout mouse embryos have severely impaired forelimb and heart morphogenesis from the earliest stages of their development. However, zebrafish embryos with compromised tbx5 function show a complete absence of pectoral fins, while heart development is disturbed at significantly later developmental stages and eye development remains to be thoroughly analysed. We identified a novel tbx5 gene in zebrafish--tbx5b--that is co-expressed with its paralogue, tbx5a, in the developing eye and heart and hypothesized that functional redundancy could be occurring in these organs in embryos with impaired tbx5a function. We have now investigated the consequences of tbx5a and/or tbx5b downregulation in zebrafish to reveal that tbx5 genes have essential roles in the establishment of cardiac laterality, dorsoventral retina axis organization and pectoral fin development. Our data show that distinct relationships between tbx5 paralogues are required in a tissue-specific manner to ensure the proper morphogenesis of the three organs in which they are expressed. Furthermore, we uncover a novel role for tbx5 genes in the establishment of correct heart asymmetry in zebrafish embryos.
CSIC-Institut de Biologia Molecular de Barcelona, Department of Developmental Biology, Parc Científic de Barcelona, C/Baldiri Reixac, 10, Barcelona 08028, Spain.
Aina
A
Pi-Roig
Enrique
E
Martin-Blanco
Carolina
C
Minguillon
D020121:5' Untranslated Regions; D058500:Animal Fins / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006321:Heart / Q000254:growth & development; D055458:Left-Right Determination Factors / Q000235:genetics / Q000378:metabolism; D060172:Morpholinos / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D010641:Phenotype; D012160:Retina / Q000254:growth & development / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D055458:Left-Right Determination Factors; C572343:Lft2 protein, zebrafish; D060172:Morpholinos; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D029961:Zebrafish Proteins
developmental biology; heart; limb; retina; tbx5; zebrafish