Hnf6 (SpHnf6, also cloned as SpOnecut) is the single sea urchin member of the ONECUT class of homeodomain transcription factors, a 483-residue protein with one CUT domain and a C-terminal homeodomain, orthologous to vertebrate HNF6/ONECUT1. Its expression in the embryo is triphasic. It is transcribed maternally and its transcripts are distributed throughout the embryo before gastrulation; during this phase it acts in the skeletogenic (large micromere/primary mesenchyme cell) lineage as an early, ubiquitously present "booster" input into the biomineralization differentiation gene battery (sm50, pm27, msp130), without being required for any of the lineage-specifying PMC regulatory genes (alx1, ets1, pmar1, tbrain) or for early micromere signaling; it is also needed for expression of the mesodermal regulator gatac. After gastrulation it becomes an early, Nodal-independent component of the oral ectoderm gene regulatory network, where it is required to maintain the oral ectoderm regulatory state; in its absence the aboral marker spec1 spreads over the whole ectoderm. Finally its expression resolves to a trapezoidal band at the oral/aboral ectoderm boundary that exactly prefigures the neurogenic ciliated band, where it persists through the end of embryogenesis and where it is required for normal ciliated band formation. The ciliary-band phase of expression is conserved in the sea star AmHNF6, and ONECUT genes in other deuterostomes are expressed in the central nervous system.
Definition: The process whose specific outcome is the progression of the ciliary band over time, from its formation to the mature structure. The ciliary band is a neurogenic band of ciliated ectodermal cells at the boundary of oral and aboral ectoderm in echinoderm and other deuterostome larvae, used for swimming and feeding.
Justification: hnf6/onecut is the canonical marker of the echinoderm ciliary band and is required for its normal formation, yet GO has no term for this larval structure; the closest available terms (nervous system development, epithelium development) do not capture it.
Parent term: anatomical structure development
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Generic DNA-binding inference from the homeodomain (IPR001356) and CUT domain (IPR003350) signatures. Correct but uninformative: Hnf6 is a ONECUT-class sequence-specific transcription factor whose loss of function abolishes activation of defined target gene sets in two separate GRNs. Reason: The domain content and the loss-of-function phenotypes support the more specific DNA-binding transcription factor activity term; bare DNA binding should be replaced rather than retained alongside it. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:15328009 The Strongylocentrotus purpuratus hnf6 (Sphnf6) gene encodes a new member of the ONECUT family of transcription factors. PMID:15230963 encodes a protein of 483 amino acids with one cut domain and a homeodomain |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: UniRule-derived nuclear localisation from the homeodomain/CUT domain content. No immunolocalisation has been published for the sea urchin protein, but a CUT homeodomain transcription factor that activates target gene transcription must act in the nucleus. Reason: Consistent with the demonstrated transcription factor function; the nucleus is the only location compatible with the gene's role. Supporting Evidence: PMID:15328009 loss-of-function analysis shows that the Hnf6 protein is a transcription factor that has multiple distinct roles in sea urchin development |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IMP PMID:15328009 SpHnf6, a transcription factor that executes multiple functi... | NEW | Summary: Hnf6 is a CUT + homeodomain (ONECUT-class) transcription factor. Morpholino knockdown abolishes activation of PMC differentiation genes (sm50, pm27, msp130) and of gatac, and prevents maintenance of the oral ectoderm regulatory state, showing that the protein functions as a transcriptional regulator of protein-coding (Pol II) genes. Direct binding to a target cis-regulatory module has not been shown, so the general factor term is proposed rather than the activator child. Reason: Core molecular function of the gene product, supported by domain architecture and loss-of-function evidence in two separate GRNs. Supporting Evidence: PMID:15328009 The Strongylocentrotus purpuratus hnf6 (Sphnf6) gene encodes a new member of the ONECUT family of transcription factors. The expression of hnf6 in the developing embryo is triphasic, and loss-of-function analysis shows that the Hnf6 protein is a transcription factor that has multiple distinct roles in sea urchin development. PMID:15661644 The sea urchin transcription factor SpHNF6 is an early activator of differentiation genes in skeletogenic lineages and regulatory genes in the oral ectoderm. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:15328009 SpHnf6, a transcription factor that executes multiple functi... | NEW | Summary: Early Hnf6 is required for activation of the PMC differentiation genes sm50, pm27 and msp130, and is modelled in the skeletogenic GRN as a ubiquitously present driver ("booster") of the differentiation gene battery. The sign of the effect is positive in every case reported. Reason: The gene product itself performs the regulatory step (activation of target gene transcription); knockdown evidence from Otim et al. and the GRN placement in Oliveri et al. agree. Supporting Evidence: PMID:15328009 Early in development, its expression is required for the activation of PMC differentiation genes such as sm50, pm27, and msp130, but not for the activation of any known PMC regulatory genes, for example, alx, ets1, pmar1, or tbrain. PMID:18413610 these differentiation genes require as drivers products of all of the now familiar components of the skeletogenic regulatory state ( alx1 , ets1 , tbr , tel , erg , hex , foxb , dri ) and in addition a factor that is at this stage ubiquitously present, Hnf6 ( 42 ). |
| GO:0070169 positive regulation of biomineral tissue development | IMP PMID:15328009 SpHnf6, a transcription factor that executes multiple functi... | NEW | Summary: The Hnf6-dependent PMC differentiation genes (sm50, pm27, msp130) encode spicule matrix and PMC surface proteins of the larval skeleton, so Hnf6 is a transcriptional activator of the biomineralization effector battery. It does not specify the skeletogenic lineage (alx1, ets1, pmar1, tbrain are Hnf6-independent) and is not involved in micromere signaling, so no lineage-specification term is proposed for this territory. Reason: Same term used for the co-acting PMC regulators (e.g. Dri) in this organism; Hnf6 performs the activating step on biomineralization genes, which satisfies the participation test for a regulation term. Supporting Evidence: PMID:15328009 Early in development, its expression is required for the activation of PMC differentiation genes such as sm50, pm27, and msp130 PMID:15661644 The sea urchin transcription factor SpHNF6 is an early activator of differentiation genes in skeletogenic lineages |
| GO:0001715 ectodermal cell fate specification | IMP PMID:15328009 SpHnf6, a transcription factor that executes multiple functi... | NEW | Summary: After gastrulation Hnf6 is one of four early, Nodal-independent components of the oral ectoderm regulatory state and is essential for maintaining oral ectoderm specification; on knockdown oral regulatory functions fail and the aboral marker spec1 spreads around the whole ectoderm. Reason: Hnf6 is a transcription factor acting within the oral ectoderm GRN itself, so it performs part of the specification process rather than merely being required for it; this is the same term carried by the co-acting oral ectoderm regulator Dri. Supporting Evidence: PMID:15328009 The second known role of hnf6 is its participation after gastrulation in the oral ectoderm gene regulatory network (GRN), in which its expression is essential for the maintenance of the state of oral ectoderm specification. PMID:19268450 knock-down of dri (Amore et al., 2003), of hnf6 (Otim et al., 2004), or of gsc (Angerer et al., 2001), all cause expression of spec1 to spread around the whole ectoderm PMID:19268450 there appear to be four early genetic components producing the initial zygotic transcriptional regulatory state in the specification of the oral ectoderm: the nodal independent hnf6, and otxΞ²1/2 genes |
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Download this section (compressed HTML)Q: Does Hnf6 bind directly to the cis-regulatory modules of sm50, pm27 or msp130, or is its "booster" input into the skeletogenic differentiation battery indirect?
Q: Which ciliated band genes depend on Hnf6, and does its ciliated band role reflect a conserved ONECUT function in neurogenic ectoderm shared with the chordate CNS expression of onecut genes?
Experiment: Mutate predicted ONECUT (CUT/homeodomain) sites in the characterised sm50 and msp130 cis-regulatory modules in reporter constructs and compare expression with wild-type constructs in normal and Hnf6-morpholino embryos; confirm occupancy by ChIP with an anti-Hnf6 antibody or tagged Hnf6 at mesenchyme blastula.
Hypothesis: Hnf6 is a direct activator of PMC biomineralization effector genes.
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