tinman (tin) encodes an NK-2 class homeodomain transcription factor, the Drosophila ortholog of vertebrate Nkx2-5. It is expressed first throughout the trunk mesoderm as a direct target of Twist, is then maintained in the dorsal mesoderm by Dpp/Smad signaling together with Tin autoregulation, and finally persists in a subset of cardioblasts. Tin binds NK-2 (TCAAGTG-type) sites in enhancers and activates target genes including bagpipe (visceral mesoderm), pannier, D-mef2, Hand, even-skipped and tinman itself. It is required for formation of the heart (dorsal vessel cardioblasts and pericardial cells, and the lymph gland from cardiogenic mesoderm), for visceral mesoderm/midgut musculature, and for specification of a subset of dorsal somatic muscle founders; later, cardioblast-intrinsic Tin specifies working myocardium versus ostial cells by repressing Dorsocross and is needed for adult heart remodeling and function. Tin is necessary but not sufficient for heart induction: it confers mesodermal competence to respond to Dpp and Wg and acts combinatorially with Pannier (GATA), Dorsocross (T-box), dTCF and pMad on cardiac enhancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that tin, an NK-2 class homeodomain protein, binds RNA polymerase II cis-regulatory sequences. Consistent with many characterized Tin-bound enhancers (tin, bap, D-mef2, pnr, Hand, eve, Toll). Reason: The NK-2 node placement is sound and tin itself has extensive direct enhancer-binding evidence (EMSA plus binding-site mutagenesis in vivo). Supporting Evidence: PMID:9034334 D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells PMID:15750188 We show that an evolutionarily conserved bap enhancer element requires combinatorial binding sites for Tin and Dpp-activated Smad proteins for its activity PMID:15870289 Tin can bind specifically to a double-stranded oligonucleotide containing this consensus site in an electrophoretic mobility shift assay, but not to an oligonucleotide containing a mutant version of this sequence |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:9694800 Smad proteins act in combination with synergistic and antago... | ACCEPT | Summary: Tin protein was recovered in a screen for proteins binding the Dpp-responsive tinman enhancer, and Tin binding sites are required for its mesodermal induction (autoregulation). Reason: Direct sequence-specific binding to a cis-regulatory module of a Pol II gene (tinman itself). Supporting Evidence: PMID:9694800 Screens for binding factors yielded Tinman itself and the Smad4 homolog Medea. We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of RNA Pol II-specific DNA-binding transcription factor activity for the NK-2 family, including tin. Reason: Core molecular function; tin is a well-established sequence-specific transcriptional activator of many target enhancers. Supporting Evidence: PMID:9034334 D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells PMID:15975941 The homeodomain protein Tinman and the GATA factors Pannier and Serpent directly activate Hand in these cell types through a minimal enhancer |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:12482712 Transcriptional integration of competence modulated by mutua... | ACCEPT | Summary: Tin binds sites in the eve mesodermal enhancer (eme) in gel-shift assays; mutation of Tin sites progressively reduces enhancer activity in vivo, and dominant-negative Tin represses eve. Reason: Direct binding plus site-dependent in vivo activation demonstrates DNA-binding TF activity. Supporting Evidence: PMID:12482712 We found that reporter gene activity was progressively reduced as more Tinman binding sites were mutated PMID:12482712 We find that Tinman and dTCF (mediating wg signaling) activate and maintain eme activity |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:15870289 Expression, regulation, and requirement of the toll transmem... | ACCEPT | Summary: Tin binds the single TCAAGTG site in the Toll dorsal vessel enhancer (EMSA) and this site is required for enhancer activity in cardioblasts. Reason: Direct binding and site-dependent transcriptional activation. Supporting Evidence: PMID:15870289 Tin can bind specifically to a double-stranded oligonucleotide containing this consensus site in an electrophoretic mobility shift assay, but not to an oligonucleotide containing a mutant version of this sequence PMID:15870289 In addition to the demonstration of Doc and Tin as activators of Toll expression in the dorsal vessel |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro homeobox-conserved-site mapping to Pol II-specific DNA-binding TF activity. Reason: Correct and consistent with experimental evidence. Supporting Evidence: PMID:9034334 D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells |
| GO:0003677 DNA binding | IDA PMID:19217429 A systematic analysis of Tinman function reveals Eya and JAK... | MODIFY | Summary: ChIP-on-chip time course of Tinman in embryos identifying direct target enhancers (e.g. eya, stat92E). Reason: DNA binding is uninformative; ChIP-chip identifies Tin occupancy at cis-regulatory enhancers of Pol II target genes, better captured by GO:0000978. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:19217429 To decipher Tinman's direct regulatory role, we performed a time course of ChIP-on-chip experiments, revealing a more prominent role in somatic muscle specification than previously anticipated |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: InterPro homeodomain mapping to DNA binding. Reason: Generic DNA binding is uninformative for a homeodomain TF with demonstrated sequence-specific binding to Pol II cis-regulatory elements; replace with GO:0000978 (already supported by IBA and IDA). Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:15870289 Tin can bind specifically to a double-stranded oligonucleotide containing this consensus site in an electrophoretic mobility shift assay, but not to an oligonucleotide containing a mutant version of this sequence |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of nuclear localization for NK-2 homeodomain TFs. Reason: Expected location of a DNA-binding transcription factor. Supporting Evidence: PMID:12482712 We found that reporter gene activity was progressively reduced as more Tinman binding sites were mutated |
| GO:0005634 nucleus | IDA PMID:12482712 Transcriptional integration of competence modulated by mutua... | ACCEPT | Summary: Nuclear localization of Tin in cardiac mesoderm cells, as assessed by immunostaining in a study of eve enhancer regulation. Reason: Consistent with function as a DNA-binding TF; deferring to curator on the figure-level evidence. Supporting Evidence: PMID:12482712 We find that Tinman and dTCF (mediating wg signaling) activate and maintain eme activity |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (Nucleus). Reason: Correct. Supporting Evidence: PMID:12482712 We found that reporter gene activity was progressively reduced as more Tinman binding sites were mutated |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based mapping to regulation of DNA-templated transcription. Reason: Correct though general; GO:0006357 and GO:0045944 more specific annotations exist. Supporting Evidence: PMID:9034334 D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of regulation of transcription by RNA Pol II. Reason: Core process for a Pol II DNA-binding TF; supported by many direct targets. Supporting Evidence: PMID:11336505 pannier is a direct transcriptional target of Tinman in the heart-forming region PMID:15975941 The homeodomain protein Tinman and the GATA factors Pannier and Serpent directly activate Hand in these cell types through a minimal enhancer |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-based inference of regulation of transcription by RNA Pol II. Reason: Correct. Supporting Evidence: PMID:9034334 D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells |
| GO:0007399 nervous system development | IEA GO_REF:0000117 | REMOVE | Summary: ARBA machine-learning inference of nervous system development. Reason: tin is a mesoderm-specific factor; this rule likely reflects neural roles of vertebrate NK-2 paralogs (e.g. Nkx2-1, Nkx2-2). The only nervous-system phenotypes reported for tin (loss of FMRFa Ap4 neuron identity) are non-autonomous, depending on retrograde BMP signals from peripheral targets, and do not indicate that tin acts in neural development. Supporting Evidence: PMID:1982429 During germband elongation all the mesodermal cells in the segmented part of the embryo express msh-2, but soon afterwards msh-2 becomes restricted to the dorsal mesoderm, which includes the primordia for the visceral musculature and the heart PMID:26092715 the Ap4 neuron is critically dependent upon the retrograde BMP signal from the axonal target for FMRFa expression |
| GO:0007419 ventral cord development | HMP PMID:26092715 Novel Genes Involved in Controlling Specification of Drosoph... | MARK AS OVER ANNOTATED | Summary: tin mutants were used as a positive control in an FMRFa-eGFP Ap4 neuron screen and lacked FMRFa/Ap4 reporter expression. Reason: Ap4 FMRFa expression depends on a target-derived retrograde BMP signal; tin acts in mesoderm, so loss of FMRFa is most plausibly a secondary consequence of missing tin-dependent mesodermal targets rather than tin executing ventral cord development. Supporting Evidence: PMID:26092715 embryos homozygous for mutations in the genes ap , dimm , gbb , tin , wit , and btn all showed <3% visible FMRFa/Ap4 cells PMID:26092715 the Ap4 neuron is critically dependent upon the retrograde BMP signal from the axonal target for FMRFa expression |
| GO:0007435 salivary gland morphogenesis | IMP PMID:16171793 Organ positioning in Drosophila requires complex tissue-tiss... | MARK AS OVER ANNOTATED | Summary: Salivary gland positioning defects in mutants lacking proper visceral/somatic mesoderm differentiation, including tin. Reason: Non-autonomous: tin is not expressed in salivary gland; it is required for visceral mesoderm, which serves as a migration substrate for the gland. Supporting Evidence: PMID:16171793 proper differentiation of the visceral and somatic mesoderm is necessary for the glands to attain their final correct position PMID:7915669 Embryos that are mutant for the tinman gene lack the appearance of visceral mesoderm and of heart primordia |
| GO:0007498 mesoderm development | IEP PMID:11486054 Patterns of gene expression during Drosophila mesoderm devel... | ACCEPT | Summary: tin identified among Twist-dependent genes in mesoderm expression profiling. Reason: Mesoderm development (subdivision of the mesoderm) is a core role of tin, well supported by genetics beyond this IEP. Supporting Evidence: PMID:11486054 Transcription profiles of twist loss-of-function embryos, embryos with ubiquitous twist expression, and wild-type embryos were compared at different developmental stages PMID:7915669 tinman seems to be one of the earliest genes required for heart development and the first gene reported for which a crucial function in the early mesodermal subdivisions has been implicated |
| GO:0007506 gonadal mesoderm development | IMP PMID:9435287 Identification of genes controlling germ cell migration and ... | KEEP AS NON CORE | Summary: tin mutants identified in a screen for genes required for germ cell migration and gonadal mesoderm formation. Reason: tin acts in parallel with zfh-1 to specify dorsolateral mesoderm derivatives including somatic gonadal precursors; a genuine but peripheral role of its mesoderm-subdivision function. Supporting Evidence: PMID:9435287 Many of these genes are involved in the development of gonadal mesoderm, the tissue that associates with germ cells to form the embryonic gonad |
| GO:0007552 metamorphosis | TAS PMID:12027431 Control of cardiac development by an evolutionarily conserve... | KEEP AS NON CORE | Summary: Review statement on tin in fly heart development, annotated to metamorphosis. Reason: Cardioblast-intrinsic Tin is required for post-embryonic heart remodeling that occurs during metamorphosis; tin participates in this as a TF but metamorphosis is a broad, non-core process. Supporting Evidence: PMID:12027431 The regulatory network that controls the formation of the primitive heart in fruit flies has been elaborated upon to form the complex multichambered heart of mammals PMID:16987868 adults exhibit severe defects in cardiac remodeling and function |
| GO:0008354 primordial germ cell migration | IMP PMID:9435287 Identification of genes controlling germ cell migration and ... | MARK AS OVER ANNOTATED | Summary: Germ cell migration defects in tin mutants. Reason: tin is not expressed in germ cells; migration defects are secondary to defective gonadal mesoderm specification. Supporting Evidence: PMID:9435287 Many of these genes are involved in the development of gonadal mesoderm, the tissue that associates with germ cells to form the embryonic gonad |
| GO:0008354 primordial germ cell migration | TAS PMID:9637912 Organogenesis: Drosophila goes gonadal. | MARK AS OVER ANNOTATED | Summary: Review of gonad organogenesis, including genes required for gonad formation and germ cell attraction. Reason: Same as IMP: germ cell migration defects are a consequence of tin function in gonadal mesoderm specification, not a role of tin in migration. Supporting Evidence: PMID:9637912 Recent work in Drosophila has built a picture of the gene activities that specify the gonad and allow it to attract germ cells |
| GO:0008406 gonad development | TAS PMID:9637912 Organogenesis: Drosophila goes gonadal. | KEEP AS NON CORE | Summary: Review of genes that specify the embryonic gonad, including tin. Reason: tin contributes to specification of somatic gonadal mesoderm; peripheral to its cardiac/visceral roles. Supporting Evidence: PMID:9637912 Recent work in Drosophila has built a picture of the gene activities that specify the gonad and allow it to attract germ cells |
| GO:0010002 cardioblast differentiation | IMP PMID:15286786 Evidence for a fruit fly hemangioblast and similarities betw... | ACCEPT | Summary: tin is required for development of all cardiogenic mesoderm, including cardioblasts. Reason: Core role: tin is required to specify cardioblasts, acting with Pnr and Doc. Supporting Evidence: PMID:15286786 are required for the development of all cardiogenic mesoderm, including the lymph gland PMID:7915669 Embryos that are mutant for the tinman gene lack the appearance of visceral mesoderm and of heart primordia |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of cell differentiation for NK homeobox TFs. Reason: Correct but general; more specific terms (cardioblast differentiation, cardiac muscle cell differentiation) are annotated. Supporting Evidence: PMID:16987868 The NK homeobox gene tinman (tin) is required for the specification of the cardiac, visceral muscle and somatic muscle progenitors in the early dorsal mesoderm of Drosophila |
| GO:0035050 embryonic heart tube development | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA inference of embryonic heart tube development. Reason: The Drosophila dorsal vessel is the embryonic heart tube; tin is required for its formation. Supporting Evidence: PMID:7915669 Embryos that are mutant for the tinman gene lack the appearance of visceral mesoderm and of heart primordia |
| GO:0035050 embryonic heart tube development | IMP PMID:15975941 Hand is a direct target of Tinman and GATA factors during Dr... | ACCEPT | Summary: tin directly activates Hand in cardioblasts and pericardial nephrocytes during dorsal vessel formation. Reason: Core process; tin mutants lack the dorsal vessel. Supporting Evidence: PMID:15975941 The homeodomain protein Tinman and the GATA factors Pannier and Serpent directly activate Hand in these cell types through a minimal enhancer PMID:15975941 Hand is activated by Tinman and Pannier in cardioblasts and pericardial nephrocytes |
| GO:0035051 cardiocyte differentiation | IMP PMID:16221729 The Dorsocross T-box genes are key components of the regulat... | ACCEPT | Summary: Genetic interactions among Doc, tin and pnr in specifying cardiac progenitors. Reason: Core: tin, with Doc and pnr, specifies cardiac cell fates. Supporting Evidence: PMID:16221729 the Dorsocross genes act in parallel with tinman to activate the expression of pannier, a cardiogenic gene encoding a Gata factor PMID:16221729 suggest that co-expression of these three genes in the cardiac mesoderm, which also involves cross-regulation, plays a major role in the specification of cardiac progenitors |
| GO:0045892 negative regulation of DNA-templated transcription | TAS PMID:12027431 Control of cardiac development by an evolutionarily conserve... | KEEP AS NON CORE | Summary: Review statement annotated to negative regulation of transcription. Reason: tin is primarily an activator; repression of Dorsocross in working myocardial cells has been shown genetically (possibly indirect), so a repressive role is supported but secondary. Supporting Evidence: PMID:12027431 The regulatory network that controls the formation of the primitive heart in fruit flies has been elaborated upon to form the complex multichambered heart of mammals PMID:16987868 This function of tin involves the repression of Dorsocross (Doc) T-box genes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:15870289 Expression, regulation, and requirement of the toll transmem... | ACCEPT | Summary: Tin activates the Toll dorsal vessel enhancer through its binding site. Reason: Direct activator function on a Pol II target. Supporting Evidence: PMID:15870289 In addition to the demonstration of Doc and Tin as activators of Toll expression in the dorsal vessel PMID:15870289 Tin can bind specifically to a double-stranded oligonucleotide containing this consensus site in an electrophoretic mobility shift assay, but not to an oligonucleotide containing a mutant version of this sequence |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEP PMID:12482712 Transcriptional integration of competence modulated by mutua... | ACCEPT | Summary: Tin and dTCF activate and maintain the eve mesodermal enhancer. Reason: Activation of eve via Tin sites; consistent with many other direct targets. Supporting Evidence: PMID:12482712 We find that Tinman and dTCF (mediating wg signaling) activate and maintain eme activity PMID:12482712 We found that reporter gene activity was progressively reduced as more Tinman binding sites were mutated |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:9694800 Smad proteins act in combination with synergistic and antago... | ACCEPT | Summary: Tin binding and synergy with Smads are required for mesodermal tinman induction (positive autoregulation). Reason: Direct positive autoregulation of a Pol II gene. Supporting Evidence: PMID:9694800 Screens for binding factors yielded Tinman itself and the Smad4 homolog Medea. We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction |
| GO:0048542 lymph gland development | IMP PMID:15286786 Evidence for a fruit fly hemangioblast and similarities betw... | KEEP AS NON CORE | Summary: tin is required for development of all cardiogenic mesoderm including the lymph gland. Reason: Lymph gland derives from tin-dependent cardiogenic mesoderm; genuine but secondary to the core cardiac specification role. Supporting Evidence: PMID:15286786 are required for the development of all cardiogenic mesoderm, including the lymph gland |
| GO:0048542 lymph gland development | IMP PMID:15975941 Hand is a direct target of Tinman and GATA factors during Dr... | KEEP AS NON CORE | Summary: Hand enhancer analysis in cardiogenic mesoderm and lymph gland. Reason: In lymph gland Hand is activated by Serpent, while Tin acts in cardioblasts and pericardial cells; tin requirement for lymph gland reflects its earlier cardiogenic mesoderm role. Supporting Evidence: PMID:15975941 The homeodomain protein Tinman and the GATA factors Pannier and Serpent directly activate Hand in these cell types through a minimal enhancer PMID:15286786 are required for the development of all cardiogenic mesoderm, including the lymph gland |
| GO:0048565 digestive tract development | IEA GO_REF:0000117 | MODIFY | Summary: ARBA inference of digestive tract development. Reason: tin role in the gut is specification of visceral mesoderm (gut musculature) via bagpipe; visceral muscle development is the accurate term. Proposed replacements: visceral muscle development Supporting Evidence: PMID:8101173 In tin mutant embryos, bap expression is not activated in the dorsal mesoderm PMID:7915669 Embryos that are mutant for the tinman gene lack the appearance of visceral mesoderm and of heart primordia |
| GO:0048615 embryonic anterior midgut (ectodermal) morphogenesis | IMP PMID:17915206 D-JNK signaling in visceral muscle cells controls the latera... | MARK AS OVER ANNOTATED | Summary: Anterior midgut morphogenesis defects in tin mutants. Reason: tin is needed for visceral mesoderm, whose absence secondarily disrupts endoderm migration and midgut morphogenesis; tin does not act in the midgut endoderm itself. Supporting Evidence: PMID:8101173 the absence of visceral mesoderm results in strong disruptions of endoderm migration and midgut morphogenesis PMID:17915206 Directional LR looping of the AMG required D-JNK signaling to be down-regulated by puc in the trunk visceral mesoderm |
| GO:0055007 cardiac muscle cell differentiation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA inference of cardiac muscle cell differentiation. Reason: Supported by experimental data (cardioblast-intrinsic Tin). Supporting Evidence: PMID:16987868 tin has a crucial role within myocardial cells that is required for the proper diversification, differentiation, and post-embryonic maturation of cardiomyocytes |
| GO:0055007 cardiac muscle cell differentiation | IMP PMID:16987868 Cardioblast-intrinsic Tinman activity controls proper divers... | ACCEPT | Summary: Cardioblast-specific removal of tin disrupts myocardial diversification and differentiation. Reason: Core: cell-intrinsic role in cardiomyocyte differentiation. Supporting Evidence: PMID:16987868 tin has a crucial role within myocardial cells that is required for the proper diversification, differentiation, and post-embryonic maturation of cardiomyocytes PMID:16987868 This function of tin involves the repression of Dorsocross (Doc) T-box genes |
| GO:0061101 neuroendocrine cell differentiation | IMP PMID:21901108 Specification of Drosophila corpora cardiaca neuroendocrine ... | KEEP AS NON CORE | Summary: Corpora cardiaca neuroendocrine cells derive from tin+ head mesoderm and are absent in tin mutants; tin plus daughterless is sufficient for ectopic CC specification. Reason: Cell-autonomous mesodermal role in a specialized lineage; tin alone is not sufficient. Supporting Evidence: PMID:21901108 The absence of CC precursors in twist and tinman mutants also strongly support this view PMID:21901108 in twi.2×PE-GAL4 UAS-tinman embryos, the population of Glass+ CC precursors was not expanded |
| GO:0061320 pericardial nephrocyte differentiation | IMP PMID:15286786 Evidence for a fruit fly hemangioblast and similarities betw... | ACCEPT | Summary: tin required for cardiogenic mesoderm including pericardial nephrocytes. Reason: Pericardial cells are part of the dorsal vessel lineage; tin activates Hand in pericardial nephrocytes. Supporting Evidence: PMID:15286786 are required for the development of all cardiogenic mesoderm, including the lymph gland PMID:15975941 Hand is activated by Tinman and Pannier in cardioblasts and pericardial nephrocytes |
| GO:0071907 determination of digestive tract left/right asymmetry | IMP PMID:17915206 D-JNK signaling in visceral muscle cells controls the latera... | MARK AS OVER ANNOTATED | Summary: Gut laterality defects in tin mutants used to remove visceral mesoderm. Reason: L/R looping depends on JNK signaling in visceral muscle; tin is required only for the existence of that tissue, not for LR determination per se. Supporting Evidence: PMID:17915206 Directional LR looping of the AMG required D-JNK signaling to be down-regulated by puc in the trunk visceral mesoderm PMID:8101173 In tin mutant embryos, bap expression is not activated in the dorsal mesoderm |
| GO:0007525 somatic muscle development | IMP PMID:8101173 tinman and bagpipe: two homeo box genes that determine cell ... | NEW | Summary: tin is required for specification of founder cells of a subset of dorsal body wall muscles; ChIP-chip shows direct Tin targets in the somatic muscle network. Reason: Not represented in GOA. tin performs the step as a transcription factor in dorsal mesoderm (direct regulation of eya and stat92E, PMID:19217429), not merely as a necessary upstream condition. Comparator: other myogenic TFs (e.g. bap/HLH54F for visceral muscle) carry tissue-level muscle development terms. Supporting Evidence: PMID:8101173 tin is required for the formation of the heart from dorsal mesoderm and for the specification of founder cells for particular body wall muscles PMID:19217429 To decipher Tinman's direct regulatory role, we performed a time course of ChIP-on-chip experiments, revealing a more prominent role in somatic muscle specification than previously anticipated PMID:19217429 In Drosophila, the family member tinman is the major regulator of cell fate within the dorsal mesoderm, including heart, visceral, and dorsal somatic muscle |
Loading supporting content…
Download this section (compressed HTML)Q: Which Tin target enhancers require Tin binding directly versus only Tin-dependent competence (e.g. via pnr/Doc induction), and does Tin act as a pioneer-like factor on cardiac enhancers given its early pan-mesodermal occupancy?
Q: Is the repression of Dorsocross in working myocardial cells direct (Tin-bound repressive enhancer) or indirect, and does it justify a negative regulation of transcription annotation?
Q: Should the visceral mesoderm-specification role of tin (bap activation) be represented by a more specific term such as visceral mesoderm cell fate specification, which is currently lacking in GO?
Experiment: Cardioblast- and adult-heart-specific degron depletion of Tin combined with CUT&RUN/ATAC to distinguish direct Tin targets maintaining adult heart function (e.g. miR-1, ion channel genes) from developmental competence targets.
Experiment: Mutate Tin sites in a Dorsocross cardiac enhancer to test whether Tin directly represses Doc in working myocardial cells.
tinman (tin) encodes a homeodomain transcription factor involved in the formation of the heart and dorsal vascular musculature.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)