T-box transcription factor 5b, the second zebrafish co-ortholog of human TBX5. It was retained from the teleost genome duplication and is paralogous to tbx5a (heartstrings). It has a T-box DNA-binding domain about 83% identical to that of tbx5a, while the rest of the protein, including a shorter C-terminal region (422 aa), is poorly conserved. It is expressed in the heart field and heart, becoming restricted to the ventricle from about 36 hpf, and in the dorsal retina. Expression starts later and is lower than tbx5a, and expression in the pectoral fin bud is weak or undetected. tbx5b is required in the heart: morphants and a frameshift mutant fail to complete cardiac looping, develop cardiac edema and die by about 6 dpf. It is also required for timely pectoral fin outgrowth and the medio-lateral migration of fin-field cells, but not for fin bud initiation, which depends on tbx5a. With tbx5a it contributes to dorsoventral patterning of the retina. Its roles are not interchangeable with those of tbx5a: tbx5a mRNA does not rescue tbx5b loss, and the reverse also fails.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: Active in chromatin (IBA). Reason: Expected of a T-box transcription factor; inherited from the Tbx2/3/4/5 node. tbx5b keeps a T-box domain (UniProt 57-237) that is 83% identical to the tbx5a T-box (PMID:39079985), and the IBA node covers the Tbx2/3/4/5 subfamily. No direct DNA-binding or reporter assay has been published for Tbx5b. But tbx5b mRNA rescues its own morphant (PMID:24759614), and an intronic frameshift allele that truncates the protein before the T-box phenocopies the morphant (PMID:30532148). Together these point to a functional T-box transcription factor. The UniProt caution that some PROSITE T-box residues are not conserved is noted, but there is no evidence of lost DNA binding. Kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding (IBA). Reason: tbx5b keeps a T-box domain (UniProt 57-237) that is 83% identical to the tbx5a T-box (PMID:39079985), and the IBA node covers the Tbx2/3/4/5 subfamily. No direct DNA-binding or reporter assay has been published for Tbx5b. But tbx5b mRNA rescues its own morphant (PMID:24759614), and an intronic frameshift allele that truncates the protein before the T-box phenocopies the morphant (PMID:30532148). Together these point to a functional T-box transcription factor. The UniProt caution that some PROSITE T-box residues are not conserved is noted, but there is no evidence of lost DNA binding. Kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart PMID:30532148 There are high levels of conservation at the amino acid level in the Tbox domain between the two paralogues but there are low levels of conservation throughout the rest of the protein [10]. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding (IEA, InterPro T-box). Reason: tbx5b keeps a T-box domain (UniProt 57-237) that is 83% identical to the tbx5a T-box (PMID:39079985), and the IBA node covers the Tbx2/3/4/5 subfamily. No direct DNA-binding or reporter assay has been published for Tbx5b. But tbx5b mRNA rescues its own morphant (PMID:24759614), and an intronic frameshift allele that truncates the protein before the T-box phenocopies the morphant (PMID:30532148). Together these point to a functional T-box transcription factor. The UniProt caution that some PROSITE T-box residues are not conserved is noted, but there is no evidence of lost DNA binding. Kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific (IBA). Reason: tbx5b keeps a T-box domain (UniProt 57-237) that is 83% identical to the tbx5a T-box (PMID:39079985), and the IBA node covers the Tbx2/3/4/5 subfamily. No direct DNA-binding or reporter assay has been published for Tbx5b. But tbx5b mRNA rescues its own morphant (PMID:24759614), and an intronic frameshift allele that truncates the protein before the T-box phenocopies the morphant (PMID:30532148). Together these point to a functional T-box transcription factor. The UniProt caution that some PROSITE T-box residues are not conserved is noted, but there is no evidence of lost DNA binding. Kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart PMID:24759614 Similarly, a full-length tbx5b form was able to rescue the jogging phenotype of tbx5b morphants when co-injected with our tbx5b MO (figure 3b; n = 117). PMID:30532148 This mutation would result in a splicing error such that the first intron is not spliced from the protein, leading to a frameshift starting at amino acid 53 and a premature stop codon after 16 incorrect amino acids (Fig 1C). |
| GO:0001708 cell fate specification | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cell fate specification (IBA, T-box family node). Reason: A broad, family-wide T-box function. No tbx5b-specific fate-specification data exist; the related tbx5a roles are in proepicardium and cardiac precursor specification. Kept as non-core, as for tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0001947 heart looping | IGI PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | ACCEPT | Summary: Heart looping (IGI, tbx5a + tbx5b double morphants). Reason: tbx5b morphants fail to complete looping, and sub-threshold double knockdown also blocks looping (PMID:24759614). The tbx5b CRISPR mutant confirms it: the heart fails to loop (PMID:30532148). Shared with tbx5a and non-redundant, since each single loss is enough. Supporting Evidence: PMID:24759614 Similarly, injection of tbx5b MO also caused heart looping defects (81%, n = 108), and these embryos displayed D-looped (52%), L-looped (16%) and no-looped (34%) cardiac morphologies PMID:24759614 Although, in agreement with a previous report [17], the severity of the phenotype was not enhanced by double knock-down, downregulation of both genes increased the penetrance of the phenotype (figure 1i). PMID:30532148 The heart fails to loop and a fluid filled edema forms surrounding the heart (Fig 1E and 1F). |
| GO:0001947 heart looping | IMP PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | ACCEPT | Summary: Heart looping (IMP, tbx5b morpholino). Reason: Seen in tbx5b morphants (PMID:24759614) and confirmed in a tbx5b frameshift mutant (PMID:30532148). Supporting Evidence: PMID:24759614 Similarly, injection of tbx5b MO also caused heart looping defects (81%, n = 108), and these embryos displayed D-looped (52%), L-looped (16%) and no-looped (34%) cardiac morphologies PMID:30532148 The heart fails to loop and a fluid filled edema forms surrounding the heart (Fig 1E and 1F). PMID:30532148 Tbx5b-/- mutants fully phenocopy the reported Tbx5b morphants[10,13]. |
| GO:0003007 heart morphogenesis | IMP PMID:23226307 MicroRNA 218 mediates the effects of Tbx5a over-expression o... | ACCEPT | Summary: Heart morphogenesis (IMP, tbx5b morpholino). Reason: tbx5b morphants have looping defects and stretched cardiac chambers. Unlike tbx5a morphants, the fins still form (PMID:23226307). Supporting Evidence: PMID:23226307 MO-Tbx5b injection caused looping defects and stretched cardiac chambers, but it did not induce Tie-2 mis-expression and lack of fins |
| GO:0003146 heart jogging | IGI PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | KEEP AS NON CORE | Summary: Heart jogging (IGI, tbx5a + tbx5b double morphants). Reason: Jogging defects are reported only in morphants (PMID:24759614), and the tbx5b mRNA rescue supports morpholino specificity. No tbx5b mutant has been scored for jogging. For tbx5a, mutants (hst and the T-box-truncating oug) jog normally (PMID:34372968), so that row is UNDECIDED in the tbx5a review. For tbx5b there is no contradicting mutant yet, so the term is kept as non-core with a morpholino-only caveat. Supporting Evidence: PMID:24759614 Similarly, tbx5b morphants displayed left as well as right and middle jogging of their linear heart tubes PMID:24759614 Similarly, a full-length tbx5b form was able to rescue the jogging phenotype of tbx5b morphants when co-injected with our tbx5b MO (figure 3b; n = 117). PMID:34372968 In such a screen we identified the oudegracht (oug) mutant in which cardiac jogging was unaffected while cardiac looping was compromised. |
| GO:0003146 heart jogging | IMP PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | KEEP AS NON CORE | Summary: Heart jogging (IMP, tbx5b morpholino). Reason: As for the IGI row: morpholino-only, with rescue by tbx5b mRNA (PMID:24759614). Not yet tested in the tbx5b mutant. Supporting Evidence: PMID:24759614 Similarly, tbx5b morphants displayed left as well as right and middle jogging of their linear heart tubes PMID:24759614 Similarly, a full-length tbx5b form was able to rescue the jogging phenotype of tbx5b morphants when co-injected with our tbx5b MO (figure 3b; n = 117). |
| GO:0003218 cardiac left ventricle formation | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Cardiac left ventricle formation (IBA). Reason: Inherited from the Tbx5 clade node, which rests on mammalian left-ventricle data. Zebrafish has a single ventricle. tbx5b is expressed in the ventricle from 36 hpf (PMID:30532148) and is needed for looping, but "left ventricle formation" does not apply to a teleost heart. The same action is taken for tbx5a. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN002601200 SUPPORTS SOURCE BUT NOT TARGET The Tbx5-clade node is sound for amniote hearts, which have a left ventricle; teleost hearts have a single ventricle, so the left-ventricle-specific term does not apply to the zebrafish descendants. MGI:MGI:102541 SUPPORTS SOURCE BUT NOT TARGET Mouse experimental evidence for left ventricle formation; the anatomy is absent in zebrafish. Supporting Evidence: PMID:30532148 Expression in the heart is similar for both paralogues until 36 hpf, when tbx5b expression is restricted to the ventricle, whereas tbx5a expression remains in both chambers of the heart [9]. |
| GO:0003677 DNA binding | IEA GO_REF:0000104 | ACCEPT | Summary: DNA binding (IEA, UniRule). Reason: Correct but general; GO:0000978 is more informative. tbx5b keeps a T-box domain (UniProt 57-237) that is 83% identical to the tbx5a T-box (PMID:39079985), and the IBA node covers the Tbx2/3/4/5 subfamily. No direct DNA-binding or reporter assay has been published for Tbx5b. But tbx5b mRNA rescues its own morphant (PMID:24759614), and an intronic frameshift allele that truncates the protein before the T-box phenocopies the morphant (PMID:30532148). Together these point to a functional T-box transcription factor. The UniProt caution that some PROSITE T-box residues are not conserved is noted, but there is no evidence of lost DNA binding. Kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: DNA-binding transcription factor activity (IEA, InterPro). Reason: tbx5b keeps a T-box domain (UniProt 57-237) that is 83% identical to the tbx5a T-box (PMID:39079985), and the IBA node covers the Tbx2/3/4/5 subfamily. No direct DNA-binding or reporter assay has been published for Tbx5b. But tbx5b mRNA rescues its own morphant (PMID:24759614), and an intronic frameshift allele that truncates the protein before the T-box phenocopies the morphant (PMID:30532148). Together these point to a functional T-box transcription factor. The UniProt caution that some PROSITE T-box residues are not conserved is noted, but there is no evidence of lost DNA binding. Kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus (IBA). Reason: Expected location of a T-box transcription factor. There is no Tbx5b-specific localization data; kept consistent with tbx5a. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleus (IEA). Reason: As for the IBA row. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm (IEA, SubCell/ARBA). Reason: The inference comes from TBX5 shuttling. Pdlim7 holds zebrafish Tbx5(a) on cytoplasmic actin (PMID:19895804), but this has not been tested for Tbx5b, whose C-terminal region differs from tbx5a's. Kept as non-core, as for tbx5a. Supporting Evidence: PMID:19895804 As expected, comparable to the chicken protein, full-length Tbx5 was detected in the nucleus but also in the cytoplasm colocalized with Pdlim7 along the actin cytoskeleton PMID:30532148 There are high levels of conservation at the amino acid level in the Tbox domain between the two paralogues but there are low levels of conservation throughout the rest of the protein [10]. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Regulation of DNA-templated transcription (IEA, InterPro). Reason: A T-box transcription factor. Knocking down tbx5b changes the expression of many genes (PMID:30532148). Supporting Evidence: PMID:30532148 Specifically, knockdown of tbx5b results in changes in somite size, in the differentiation of vasculature progenitors and in later patterning of trunk blood vessels. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II (IBA). Reason: As above. tbx5a and tbx5b loss affect partly different target sets (for example bmp4 changes only after tbx5a loss), which suggests different transcriptional networks (PMID:30532148). Supporting Evidence: PMID:30532148 In the heart, expression of vcana is expanded in embryos deficient in either Tbx5a or Tbx5b, but expression of bmp4 is only restricted in embryos deficient in Tbx5a, not in embryos deficient in Tbx5b[10]. PMID:30532148 Specifically, knockdown of tbx5b results in changes in somite size, in the differentiation of vasculature progenitors and in later patterning of trunk blood vessels. |
| GO:0007389 pattern specification process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pattern specification process (IBA). Reason: tbx5b helps pattern the dorsal retina (with tbx5a) and the medio-lateral migration of fin-field cells (PMID:24759614, PMID:34756968). Broad but correct. Supporting Evidence: PMID:24759614 suggesting that tbx5 paralogues act redundantly in the dorsal retina to ensure efnb2a expression in this territory. PMID:34756968 We show here that loss of Tbx5b function affects initial ML directed movements so that fin field cells fail to migrate laterally but continue to converge along the AP axis. |
| GO:0007507 heart development | IMP PMID:23441045 Zebrafish tbx5 paralogs demonstrate independent essential re... | ACCEPT | Summary: Heart development (IMP, tbx5b morpholino). Reason: tbx5b is needed in the heart for embryonic survival (PMID:23441045). This is confirmed genetically: tbx5b frameshift mutants fail to loop, develop cardiac edema and die by 6 dpf (PMID:30532148). Supporting Evidence: PMID:23441045 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. PMID:30532148 The heart fails to loop and a fluid filled edema forms surrounding the heart (Fig 1E and 1F). PMID:30532148 By 6 days, both mutants and morphant embryos die, possibly as a result of the severe heart defects. |
| GO:0007507 heart development | IMP PMID:23441045 Zebrafish tbx5 paralogs demonstrate independent essential re... | ACCEPT | Summary: Heart development (IMP, second tbx5b morpholino). Reason: As for the first morpholino. Two morpholinos and a mutant agree (PMID:23441045, PMID:30532148). Supporting Evidence: PMID:23441045 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. PMID:30532148 Tbx5b-/- mutants fully phenocopy the reported Tbx5b morphants[10,13]. |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: Anatomical structure morphogenesis (IEA, ARBA). Reason: Broad but true: tbx5b is needed for heart and pectoral fin morphogenesis (PMID:30532148). Supporting Evidence: PMID:30532148 The heart fails to loop and a fluid filled edema forms surrounding the heart (Fig 1E and 1F). PMID:30532148 Tbx5b-/- mutants also exhibit similar fin defects to the Tbx5b morphants. |
| GO:0021554 optic nerve development | IGI PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | KEEP AS NON CORE | Summary: Optic nerve development (IGI, tbx5a + tbx5b double morphants). Reason: Only double morphants have a thinner optic nerve (PMID:24759614). A shared, additive, morpholino-only retinal role, the same as for tbx5a. Supporting Evidence: PMID:24759614 Moreover, and in agreement with both tbx5 genes acting redundantly to ensure proper optic nerve formation, double-morphant embryos showed a significantly thinner optic nerve (figure 4n). |
| GO:0033339 pectoral fin development | IMP PMID:23441045 Zebrafish tbx5 paralogs demonstrate independent essential re... | ACCEPT | Summary: Pectoral fin development (IMP, tbx5b morpholino). Reason: tbx5b is needed for normal pectoral fin outgrowth and shape, but not for fin bud initiation (which needs tbx5a). tbx5b morphants have small, delayed fins, and fin-field cells fail to migrate medio-laterally (PMID:24759614, PMID:34756968). A tbx5b frameshift mutant reproduces the fin defect (PMID:30532148). Whether tbx5b is expressed in the fin at all is disputed (not detected in PMID:19925885; low levels in PMID:23441045), so this role may be partly non-cell-autonomous. This asymmetry in fin roles is copy-specific and should be kept. Supporting Evidence: PMID:23441045 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. PMID:30532148 Tbx5b-/- mutants also exhibit similar fin defects to the Tbx5b morphants. |
| GO:0033339 pectoral fin development | IMP PMID:23441045 Zebrafish tbx5 paralogs demonstrate independent essential re... | ACCEPT | Summary: Pectoral fin development (IMP, second tbx5b morpholino). Reason: tbx5b is needed for normal pectoral fin outgrowth and shape, but not for fin bud initiation (which needs tbx5a). tbx5b morphants have small, delayed fins, and fin-field cells fail to migrate medio-laterally (PMID:24759614, PMID:34756968). A tbx5b frameshift mutant reproduces the fin defect (PMID:30532148). Whether tbx5b is expressed in the fin at all is disputed (not detected in PMID:19925885; low levels in PMID:23441045), so this role may be partly non-cell-autonomous. This asymmetry in fin roles is copy-specific and should be kept. Supporting Evidence: PMID:23441045 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. PMID:34756968 Zebrafish deficient in tbx5a lack pectoral fin buds, whereas zebrafish deficient in tbx5b exhibit misshapen pectoral fins, showing that both paralogues function in fin development. |
| GO:0033339 pectoral fin development | IMP PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | ACCEPT | Summary: Pectoral fin development (IMP, tbx5b morpholino, PMID:24759614). Reason: tbx5b is needed for normal pectoral fin outgrowth and shape, but not for fin bud initiation (which needs tbx5a). tbx5b morphants have small, delayed fins, and fin-field cells fail to migrate medio-laterally (PMID:24759614, PMID:34756968). A tbx5b frameshift mutant reproduces the fin defect (PMID:30532148). Whether tbx5b is expressed in the fin at all is disputed (not detected in PMID:19925885; low levels in PMID:23441045), so this role may be partly non-cell-autonomous. This asymmetry in fin roles is copy-specific and should be kept. Supporting Evidence: PMID:24759614 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 PMID:24759614 Taken together, we show that pectoral fin development has a different requirement for each of the tbx5 paralogues: tbx5a function is required for the earliest steps of initiation of fin outgrowth, whereas tbx5b functions later to ensure properly timed and sustained fin outgrowth. PMID:30532148 Tbx5b-/- mutants also exhibit similar fin defects to the Tbx5b morphants. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Positive regulation of DNA-templated transcription (IEA, InterPro). Reason: Tbx5 proteins act as activators, and tbx5b is a functional T-box factor (see MF rows). There is no tbx5b-specific reporter data. Supporting Evidence: PMID:39079985 The T-box domain of Tbx5b shares only 83% sequence identity with its Tbx5a counterpart |
| GO:0048794 swim bladder development | IGI NOT PMID:30352852 Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates c... | ACCEPT | Summary: NOT swim bladder development (negated). Reason: tbx5a/tbx5b single and double morphants form a swim bladder, so the pair is not required for swim bladder specification (PMID:30352852). Accepted as a negative result. tbx5b mutants do fail to inflate the swim bladder (PMID:30532148). Inflation is a later, physiological step that is probably secondary to heart failure, so it does not contradict the NOT. Morpholino-only for the formation claim. Supporting Evidence: PMID:30352852 However, we find that although Tbx5 is required for lung formation, tbx5a / b is not required for SB formation in the zebrafish. PMID:30352852 To address potential redundancy, we utilized published MOs designed to target tbx5a , tbx5b , or tbx5a and tbx5b ( 47 , 48 ). PMID:30532148 Additionally, unlike their wildtype siblings, the swim bladder of Tbx5b-deficient embryos does not inflate. |
| GO:0048794 swim bladder development | IMP NOT PMID:30352852 Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates c... | ACCEPT | Summary: NOT swim bladder development (negated). Reason: tbx5a/tbx5b single and double morphants form a swim bladder, so the pair is not required for swim bladder specification (PMID:30352852). Accepted as a negative result. tbx5b mutants do fail to inflate the swim bladder (PMID:30532148). Inflation is a later, physiological step that is probably secondary to heart failure, so it does not contradict the NOT. Morpholino-only for the formation claim. Supporting Evidence: PMID:30352852 However, we find that although Tbx5 is required for lung formation, tbx5a / b is not required for SB formation in the zebrafish. PMID:30352852 To address potential redundancy, we utilized published MOs designed to target tbx5a , tbx5b , or tbx5a and tbx5b ( 47 , 48 ). PMID:30532148 Additionally, unlike their wildtype siblings, the swim bladder of Tbx5b-deficient embryos does not inflate. |
| GO:0060042 retina morphogenesis in camera-type eye | IGI PMID:24759614 Distinct tissue-specific requirements for the zebrafish tbx5... | KEEP AS NON CORE | Summary: Retina morphogenesis in camera-type eye (IGI, double morphants). Reason: Dorsal efnb2a shrinks significantly only in tbx5a + tbx5b double morphants (PMID:24759614). This is shared dorsoventral patterning of the retina, the same as for tbx5a, and morpholino-only. Supporting Evidence: PMID:24759614 suggesting that tbx5 paralogues act redundantly in the dorsal retina to ensure efnb2a expression in this territory. |
| GO:0060429 epithelium development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Epithelium development (IEA, ARBA). Reason: No zebrafish evidence; an ARBA machine-learning generalization. Treated the same way in tbx5a. |
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Download this section (compressed HTML)Q: Is tbx5b expressed in pectoral fin-field cells at all? If not, does it act on fin-field migration non-cell-autonomously, for example from the adjacent heart field or somites?
Q: Is the failure of tbx5a mRNA to rescue tbx5b morphants due to protein divergence (the C-terminal region, T-box substitutions) or to dose, timing and ubiquitous expression of injected mRNA?
Q: Does the tbx5b frameshift allele (intron-1 insertion, PTC) trigger nonsense-mediated decay and upregulation of tbx5a?
Experiment: Compare DNA-binding specificity (SELEX or CUT&RUN) and transactivation of Tbx5a and Tbx5b on the same T-box reporters, and swap the coding sequences between the loci by knock-in.
Hypothesis: Tbx5b has diverged at the protein level from Tbx5a.
Type: biochemical comparison and coding-sequence swap
Experiment: Score jogging (myl7, 26 hpf) in tbx5b mutants and in a promoter-less tbx5b allele, with measurement of tbx5a transcript levels.
Hypothesis: tbx5b is required for heart jogging.
Type: mutant phenotyping
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Download this section (compressed HTML)Loading supporting content…
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