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Distinct tissue-specific requirements for the zebrafish tbx5 genes during heart, retina and pectoral fin development.

Pi-Roig A, Martin-Blanco E, Minguillon C - Open Biol (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: CSIC-Institut de Biologia Molecular de Barcelona, Department of Developmental Biology, Parc Científic de Barcelona, C/Baldiri Reixac, 10, Barcelona 08028, Spain.

ABSTRACT
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.

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tbx5b knock-down causes a delay in pectoral fin growth. (a,i,q) Pectoral fin morphology at 3 dpf. Dorsal views are shown with anterior to the top. (b–h) Expression of the developing pectoral fin markers in control (ctrl) MO-injected embryos. (c′–h′) Higher magnifications of (c–h). (j–p) Pectoral fin markers expression in tbx5b-morphant embryos. (k′–p′) Higher magnifications of (k–p). (r,s) tbx5a morphants. (t) Model for the differential requirements for the tbx5 genes during pectoral fin development. b–h, j–p,r,s are dorsal views with anterior to the left. c′–h′,k′–p′ are lateral views with anterior to the left.
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RSOB140014F5: tbx5b knock-down causes a delay in pectoral fin growth. (a,i,q) Pectoral fin morphology at 3 dpf. Dorsal views are shown with anterior to the top. (b–h) Expression of the developing pectoral fin markers in control (ctrl) MO-injected embryos. (c′–h′) Higher magnifications of (c–h). (j–p) Pectoral fin markers expression in tbx5b-morphant embryos. (k′–p′) Higher magnifications of (k–p). (r,s) tbx5a morphants. (t) Model for the differential requirements for the tbx5 genes during pectoral fin development. b–h, j–p,r,s are dorsal views with anterior to the left. c′–h′,k′–p′ are lateral views with anterior to the left.

Mentions: Although we had not previously observed tbx5b expression in developing pectoral fins [16], others have recently described it in the pectoral fin bud mesenchyme of 36 hpf embryos [17]. In agreement with tbx5b playing a role during zebrafish pectoral fin morphogenesis, tbx5b morphants had smaller pectoral fins when compared with control embryos at 3 dpf (figure 5a,i; [17]), which is reminiscent of the phenotypes observed upon subtle downregulation of tbx5a function [14,15] or downregulation of tbx5 target genes [35]. To get further insight into where in the limb developmental pathway tbx5b function is required, we used a series of markers to assess the state of the two tissues required for and involved in the process of fin outgrowth: the fin mesenchyme and the overlying fin ectoderm. Briefly, bi-directional fibroblast growth factor (FGF) signals emanate from and are received by both tissues, creating a positive feedback loop that is required to sustain pectoral fin outgrowth [10].Figure 5.


Distinct tissue-specific requirements for the zebrafish tbx5 genes during heart, retina and pectoral fin development.

Pi-Roig A, Martin-Blanco E, Minguillon C - Open Biol (2014)

tbx5b knock-down causes a delay in pectoral fin growth. (a,i,q) Pectoral fin morphology at 3 dpf. Dorsal views are shown with anterior to the top. (b–h) Expression of the developing pectoral fin markers in control (ctrl) MO-injected embryos. (c′–h′) Higher magnifications of (c–h). (j–p) Pectoral fin markers expression in tbx5b-morphant embryos. (k′–p′) Higher magnifications of (k–p). (r,s) tbx5a morphants. (t) Model for the differential requirements for the tbx5 genes during pectoral fin development. b–h, j–p,r,s are dorsal views with anterior to the left. c′–h′,k′–p′ are lateral views with anterior to the left.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043114&req=5

RSOB140014F5: tbx5b knock-down causes a delay in pectoral fin growth. (a,i,q) Pectoral fin morphology at 3 dpf. Dorsal views are shown with anterior to the top. (b–h) Expression of the developing pectoral fin markers in control (ctrl) MO-injected embryos. (c′–h′) Higher magnifications of (c–h). (j–p) Pectoral fin markers expression in tbx5b-morphant embryos. (k′–p′) Higher magnifications of (k–p). (r,s) tbx5a morphants. (t) Model for the differential requirements for the tbx5 genes during pectoral fin development. b–h, j–p,r,s are dorsal views with anterior to the left. c′–h′,k′–p′ are lateral views with anterior to the left.
Mentions: Although we had not previously observed tbx5b expression in developing pectoral fins [16], others have recently described it in the pectoral fin bud mesenchyme of 36 hpf embryos [17]. In agreement with tbx5b playing a role during zebrafish pectoral fin morphogenesis, tbx5b morphants had smaller pectoral fins when compared with control embryos at 3 dpf (figure 5a,i; [17]), which is reminiscent of the phenotypes observed upon subtle downregulation of tbx5a function [14,15] or downregulation of tbx5 target genes [35]. To get further insight into where in the limb developmental pathway tbx5b function is required, we used a series of markers to assess the state of the two tissues required for and involved in the process of fin outgrowth: the fin mesenchyme and the overlying fin ectoderm. Briefly, bi-directional fibroblast growth factor (FGF) signals emanate from and are received by both tissues, creating a positive feedback loop that is required to sustain pectoral fin outgrowth [10].Figure 5.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: CSIC-Institut de Biologia Molecular de Barcelona, Department of Developmental Biology, Parc Científic de Barcelona, C/Baldiri Reixac, 10, Barcelona 08028, Spain.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus