Cited by 69Marine Invertebrate Physiology and EcologyDevelopmental Biology and Gene RegulationGenomics and Chromatin Dynamics

Evolutionary aspects of developmentally regulated helix-loop-helix transcription factors in striated muscle of jellyfish

Open access
Müller, Peter, Seipel, Katja, Yanze, Nathalie, Reber-Müller, Susanne, Streitwolf-Engel, Ruth, Stierwald, Michael, Spring, J.ürg, Schmid, Volker·2003·Developmental Biology

Abstract

The function of basic helix-loop-helix (bHLH) proteins in cell differentiation was shown to be conserved from Drosophila to vertebrates, exemplified by the function of MyoD in striated muscle differentiation. In phylogeny striated muscle tissue appears first in jellyfish and the question of its evolutionary position is controversially discussed. For this reason we have studied the developmental role of myogenic bHLH genes in medusa development. Based on their dimerization ability, four genes of the bHLH family of transcription factors were isolated from the hydrozoan jellyfish Podocoryne carnea. While the proteins Id and Ash group with cognate family members from bilaterians, Net-like and JellyD1 could not be unequivocally classified. Id is expressed during the medusa budding process and in the adult medusa, Ash and Net-like are expressed in all life cycle stages from egg to adult medusa and JellyD1 is expressed in the blastula and gastrula stages, the planula larva, and in late medusa bud stages. The dimerization specificity, the expression pattern, and the conservation of two residues specific for a MyoD bHLH domain suggest that JellyD1 is related to an ancestral MyoD gene. Id, Net-like, and JellyD1 are either expressed in the entocodon or its derived tissues, the striated and smooth muscle of the bell. These findings strengthen the hypothesis that the entocodon is a mesoderm-like structure and that the common ancestor of Cnidaria and Bilateria was more complex in cell-type architecture and body organization than commonly thought.

Integrity signals

Registry

Crossref · 10.1016/s0012-1606(02)00091-x

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 78 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    JellyD1 is expressed in the blastula and gastrula stages, the planula larva, and late medusa bud stages.

    “JellyD1 is expressed in the blastula and gastrula stages, the planula larva, and in late medusa bud stages.”
    Quote in the paperSubstantial claim
  • Findingown data

    Four genes from the basic helix-loop-helix family of transcription factors were isolated from the hydrozoan jellyfish Podocoryne carnea.

    “four genes of the bHLH family of transcription factors were isolated from the hydrozoan jellyfish Podocoryne carnea.”
    Quote in the paperSubstantial claim
  • Findingnone given

    The founding insect achaete and scute proteins and all other insect family members have an insert in the loop region that is absent in Podocoryne and other phyla.

    “Interestingly, the founding members achaete and scute as well as all other insect family members have an insert in the loop region that is not present in Podocoryne or other phyla.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The interaction trap screen identified the HLH transcription factor Id and the bHLH factors Ash, Net-like, and JellyD1.

    “The interaction trap screen of a Podocoryne cDNA library led to the identification of the HLH transcription factor Id, and the bHLH factors Ash, Net-like, and JellyD1.”
    Quote in the paperSubstantial claim
  • Findingown data

    Id, Net-like, and JellyD1 are expressed in the entocodon or its derived tissues, the striated and smooth muscle of the bell.

    “Id, Net-like, and JellyD1 are either expressed in the entocodon or its derived tissues, the striated and smooth muscle of the bell.”
    Quote in the paperSubstantial claim
  • May combine two claims. 74
  • Classified as probably not a substantial claim. 16
  • The quote only partly states this claim. 2
  • May combine two claims.

    Findingown data

    The Ash bHLH domain has 65% identity with mouse Ash1, 59% with Drosophila achaete or scute, and 52% with the C. elegans homologue T24B8.6.

    “showing 65% sequence identity with mouse Ash1, 59% with Drosophila achaete or scute, and 52% with the C. elegans homologue T24B8.6.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Id was found eight times, whereas the other three transcription factors were isolated only once in the screen.

    “Id was found eight times, whereas the other three transcription factors were isolated only once in the screen.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Id was also isolated independently using mouse MyoD1 as bait.

    “Id was also isolated independently using mouse MyoD1 as bait.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Podocoryne Id has 32-43% identity to Drosophila emc and the four mouse Id family members Id1-4, significantly higher than to all bHLH proteins with a basic domain.

    “Sequence similarities are relatively low with only 32-43% identity to Drosophila emc and the four mouse Id family members Id1-4 but significantly higher than to all bHLH proteins with a basic domain.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingcitation

    Podocoryne Ash aligns over its entire length with Hydra CnASH at 60% identity, and their bHLH regions are 87% identical.

    “The sequence can be aligned over the entire length with the Hydra CnASH protein (Grens et al., 1995) with 60% of sequence identity.Within their bHLH regions the two proteins are 87% iden- tical.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Grens et al., 1995

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Podocoryne Ash was isolated as a full-length clone and encodes a 158-amino-acid protein with the bHLH domain spanning amino acids 67 to 120.

    “Podocoryne Ash was isolated as a full-length clone and encodes a protein of 158 amino acids with the bHLH domain spanning amino acids 67 to 120”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    The 107-amino-acid Podocoryne Id fragment is encoded by a partial cDNA clone and lacks the basic region N-terminal to the HLH domain from amino acids 24 to 64.

    “The 107 amino acid fragment of Podocoryne Id is encoded by a partial cDNA clone and is lacking the basic region Nterminal to the HLH domain from amino acids 24 to 64”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    A total of 3.4 × 10^7 yeast clones were screened, and 518 clones grew on selective media.

    “A total of 3.4 ϫ 10 7 yeast clones were screened and 518 clones grew on selective media.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    JellyD1, Ash, and Id were isolated with the Drosophila daughterless bait, while Net-like was isolated using JellyD1 as bait.

    “JellyD1, Ash, and Id were isolated with the Drosophila daughterless bait while the Net-like transcription factor was isolated using JellyD1 as bait.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Except for Net-like, all gene products interact with Drosophila daughterless, and all four interact with vertebrate MyoD.

    “Except for Net-like, all gene products were found to interact with Drosophila daughterless and all four were found to interact with vertebrate MyoD.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    HLH domains show high sequence conservation within each subfamily but only moderate conservation between subfamilies.

    “The HLH domains from the different protein subfamilies show a high degree of sequence conservation within each subfamily but only moderate conservation between subfamilies”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Id is expressed during medusa budding and in the adult medusa.

    “Id is expressed during the medusa budding process and in the adult medusa”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingcitation

    Podocoryne Net-like lacks a proline-rich region thought to be important for transcriptional repression in Drosophila Net and lacks a leucine zipper domain characteristic of Myc and Max family members.

    “Furthermore Podocoryne Net-like does not contain a proline-rich region thought to be important for transcriptional repression in Drosophila Net (Brentrup et al., 2000) or a leucine zipper domain characteristic for Myc and Max family members.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Brentrup et al., 2000

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Myofiber differentiation rises sharply after stage 5 and stops after stage 8, when proliferation in the striated muscle layer has ceased.

    “Myofiber differentiation strongly increases after stage 5 and ends after stage 8 when cell proliferation in the striated muscle layer has stopped (Schmid, 1972).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schmid, 1972

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Podocoryne Ash interacted strongly with Id when fused to LexA, whereas the same proteins expressed from the opposite vectors interacted only weakly.

    “For example, Podocoryne Ash interacted strongly with Id when fused to LexA, whereas the same proteins expressed from the opposite vectors interacted only weakly”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingown data

    Podocoryne Twist interacted with JellyD1 and Id but not with the mouse or Xenopus MyoD fusion proteins.

    “Moreover, Podocoryne Twist interacted with JellyD1 and Id but not with the mouse or Xenopus MyoD fusion proteins”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingown data

    Net-like is a 148-amino-acid protein with the bHLH domain spanning amino acids 49 to 99.

    “The gene encodes a 148 amino acid protein with the bHLH domain spanning amino acids 49 to 99”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    JellyD1 expression is very weak in gastrulation, stronger in the planula larva, and restarts in the late medusa bud stages.

    “JellyD1 expression is very weak in gastrulation, stronger in the planula larva, and restarts again in the late medusa bud stages”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    RT-PCR demonstrates the presence of Ash and Net-like transcripts in the unfertilized egg, in all stages of the life cycle, and in all medusa bud stages.

    “Expression analysis by RT-PCR demonstrates the presence of the Ash and Net-like transcripts in the unfertilized egg, in all stages of the life cycle and in all medusa bud stages”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    JellyD1 interacted with daughterless and with Id.

    “As expected for a MyoD-like factor, JellyD1 interacted with Da and with Id.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingcitation

    From stage 9 onward and in the adult medusa, no DNA replication occurs in bell-forming tissues, but proliferation continues in the manubrium and tentacle bulbs.

    “From stage 9 on and in the adult medusa no DNA replication occurs in the tissues which form the bell; however, cell proliferation is observed in the manubrium and in the tentacle bulbs (Schmid, 1972;Spring et al., 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Schmid, 1972

      Not checked in the free run.

    • cites Spring et al., 2000 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    JellyD1 is a 109-amino-acid protein with the bHLH domain spanning amino acids 24 to 76.

    “JellyD1 is a protein of 109 amino acids with the bHLH domain spanning amino acids 24 to 76.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Interactions between JellyD1 and Podocoryne Twist were detected, while both vertebrate MyoD constructs did not interact with Podocoryne Twist.

    “Surprisingly, interactions between JellyD1 and Podocoryne Twist were detected while both MyoD constructs from vertebrates did not interact with Podocoryne Twist.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingown data

    JellyD1 homodimerized and interacted with the mouse and Xenopus MyoD homologues.

    “Homodimerization of JellyD1 and interactions with the mouse as well as the Xenopus MyoD homologues were”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingnone given

    The entocodon cavity is fully closed off until stage 5, and from stage 6-7 a velar opening forms through which growing tentacles enter the cavity.

    “Up to stage 5 the entocodon cavity is completely sealed off from the outside but from stage 6 -7 on the velar opening forms through which the growing tentacles are pushed into the entocodon cavity.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Podocoryne Id formed heterodimers with all tested proteins but did not form homodimers.

    “Podocoryne Id was able to form heterodimers with all tested proteins, but no homodimers”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingown data

    Net-like interacted with JellyD1, Id, and vertebrate MyoD constructs, but no interaction with Drosophila daughterless was detected.

    “Net-like not only interacts with JellyD1 but also with Id and vertebrate MyoD constructs, while no interaction with the Drosophila daughterless protein could be detected.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingcitation

    Podocoryne Ash formed heterodimers with the Podocoryne transcriptional repressor Id, consistent with the interaction of achaete-scute and Id family members in Drosophila.

    “Furthermore, it formed heterodimers with the Podocoryne transcriptional repressor Id, consistent with the interaction of members of the achaete-scute and Id families in Drosophila”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cabrera et al., 1994

      Not checked in the free run.

    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Tentacle bulbs and tentacles differentiate distally without any cellular contribution from the entocodon.

    “Also distally the tentacle bulbs and tentacles will differentiate, however, without any cellular contribution from the entocodon.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Net-like is most similar to the Drosophila bHLH transcriptional repressor Net at 35% identity and almost equally similar to members of the Myc and Max families.

    “When compared to the databases, the Net-like protein is most similar to the Drosophila bHLH transcriptional repressor Net (35% identity; Brentrup et al., 2000) and almost equally similar to the members of the Myc and Max families”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Brentrup et al., 2000

      Not checked in the free run.

    • cites Grandori et al., 2000 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Findingown data

    Occasionally, in a few old larvae, some cells at the most anterior pole showed Id staining.

    “Occasionally, in a few old larvae some cells at the most anterior pole showed some staining”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    JellyD1 also shows sequence similarities to the bHLH domains of Hand and Hen family members, and phylogenetic analysis cannot assign it to a specific subfamily.

    “However, sequence similarities are also seen with the bHLH domains of members of the Hand and Hen families and phylogenetic analysis cannot assign JellyD1 to a specific subfamily”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    JellyD1 contains the two crucial amino acid residues in the correct position in its basic region, while the lysine is replaced by a glutamic acid residue.

    “JellyD1 contains these two crucial amino acid residues in the correct position in its basic region, while the lysine is replaced by a glutamic acid residue.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    The late bud stages become a functional medusa at stage 9, and within minutes the bell mesoglea swells.

    “The transformation of the late bud stages into a functional medusa occurs at stage 9. Within a few minutes the mesoglea of the bell swells (Schmid, 1972).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schmid, 1972

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    JellyD1 alanine 32 and threonine 33 correspond to alanine 114 and threonine 115 in mouse MyoD1, while lysine 124 is not conserved.

    “Alanine 32 and threonine 33 correspond to alanine 114 and threonine 115 in mouse MyoD1, while lysine 124 is not conserved”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Podocoryne Twist did not bind to daughterless, while Drosophila Twist and daughterless interacted.

    “The Podocoryne Twist protein, despite its high level of sequence conservation, did not bind to Da, while Drosophila Twist and Da interacted”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Castanon et al., 2001

      Not checked in the free run.

    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Findingown data

    Id staining occurs throughout bud development, beginning in the distal endoderm of the first bud stage and later in the manubrium anlage and radial canal endoderm.

    “In situ analysis (Fig. 5) demonstrates that Id staining is present throughout bud development, starting in the distal endoderm of the very first bud stage and from then on in the manubrium anlage (feeding and sex organ) and in the endoderm of the radial canals.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    The stage 2 entocodon has no Net-like staining, but from later stages onward the entocodon and differentiating and mature bell muscle stain.

    “The very young entocodon of stage 2 shows no staining but in all later stages the entocodon and the differentiating and fully developed muscle of the bell stain.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    At stage 5-6, Ash staining appears in interradial ectoderm cells and in the manubrium anlage endoderm.

    “At stage 5-6 cells in the interradial ectoderm and in the endoderm of the manubrium anlage stain.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    When the entocodon cavitates at stage 3-4, Id staining increases and stays strong through striated and smooth muscle differentiation, persisting into late bud stages 8-10.

    “When the entocodon forms a cavity at stage 3-4, entocodal staining increases and remains strong throughout the differentiation process of the striated and smooth muscle and even persists into the late bud stage 8 -10 when the muscle is fully differentiated.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    JellyD1 interacts with itself and with Da, Id, MyoD, Net-like, and Twist, while Ash interacts only with Da and Id.

    “JellyD1 interacts with itself and with Da, Id, MyoD, Net-like, and Twist, while Ash interacts only with Da and Id.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    No Ash staining was seen in plate cells or developing muscle tissue.

    “No staining was observed in the plate cells and the developing muscle tissue.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Consistent with the idea that JellyD1 is a MyoD homologue, the gene is absent in early entocodon stages 1-4 and appears later when cells begin forming striated myofibrils.

    “In accordance with the hypothesis that JellyD1 represents a MyoD homologue the gene is not expressed in the early stages of entocodon development (stages 1-4, Figs.3B and 5) but later when the cells start to differentiate the striated myofibrils.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    JellyD1 staining first appears in the distal manubrium endoderm, developing gonads, and differentiating striated and smooth bell muscle.

    “The first staining is detected in the distal endoderm of the manubrium, the developing gonads, and in the differentiating striated and smooth muscle of the bell.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingcitation

    Twist is weakly expressed in differentiating muscle but strongly expressed in plate cells.

    “Twist, another negative regulator of myogenesis in Bilateria, is only weakly expressed in the differentiating muscle but strongly in the plate cells (control in Fig. 5; Spring et al., 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Spring et al., 2002

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Findingown data

    Net-like staining is also present in the gonads.

    “Staining is also found in the gonads.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Drosophila daughterless has been used successfully in cross-phyla screens and interacts with the Hydra achaete-scute homologue CnASH.

    “The Drosophila E-protein homologue daughterless has been used successfully in cross-phyla screens (Lee et al., 1995) and interacts with a cnidarian bHLH factor, the Hydra achaete-scute homologue CnASH (Grens et al., 1995).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Lee et al., 1995

      Not checked in the free run.

    • cites Grens et al., 1995

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hydra CnASH dimerizes with Drosophila Da and binds in vitro to the E-box consensus sequence specific for Drosophila achaete-scute complex proteins.

    “The CnASH protein from Hydra is able to dimerize with the Drosophila protein Da and binds in vitro to the E-box consensus sequence specific for the Drosophila achaetescute complex proteins”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Grens et al., 1995

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Id family members heterodimerize with many different bHLH proteins and antagonize their functions, forming complexes incapable of binding DNA.

    “The Id protein family members heterodimerize with many different bHLH proteins and thus antagonize their functions, resulting in a form that is incapable of binding DNA”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Norton, 2000

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Podocoryne cognates of bilaterian genes specific for mesoderm formation and myogenesis are highly conserved and show comparable expression patterns.

    “Recently it has been demonstrated that the Podocoryne cognates of bilaterian genes specific for mesoderm formation and myogenesis are highly conserved and show comparable expression patterns.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Spring et al., 2000 source

      Not checked in the free run.

    • cites Spring et al., 2002

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mouse MyoD1 has been reported to interact with Twist, but this interaction is not a conventional HLH-HLH interaction and also requires the basic domains of the two proteins.

    “Mouse MyoD1 has been reported to interact with Twist; however, the interaction is not a result of a conventional HLH-HLH interaction but also requires the basic domains of the two proteins”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hamamori et al., 1997

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The volume increase unfolds the bell tissues, moves the tentacles outward, and triggers rhythmic contractions in the striated muscle that free the medusa from the mother polyp.

    “The increase in volume unfolds the bell tissues causing the tentacles to attain their external position and activates rhythmic contractions in the striated muscle, a process that liberates the medusa from the mother polyp.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Members of the MyoD family were reported to form only heterodimers.

    “unexpected since members of the MyoD family were reported to form only heterodimers”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Hu et al., 1992

      Not checked in the free run.

    • cites Lassar et al., 1991

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Podocoryne Ash did not form homodimers or interact with JellyD1 and Twist, indicating that it can discriminate between different bHLH proteins.

    “Formation of homodimers or interactions with tissue-specific transcription factors such as JellyD1 and Twist could not be detected, indicating that Podocoryne Ash is able to discriminate between the different bHLH proteins.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Premisecitation

    E-12 proteins do not homodimerize, which is consistent with the results obtained with the Drosophila E-protein homologue daughterless.

    “Homodimerization of the E-12 proteins does not occur (Maleki et al., 1997), which is consistent with our results with the Drosophila E-protein homologue daughterless”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Maleki et al., 1997

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    During medusa bud development, the entocodon forms a cavity that becomes the future subumbrellar space.

    “During this process the entocodon forms a cavity, the future subumbrellar space”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    At stage 4, the four radial canal tubes that were connected at stage 3 become separated by the growing bud but remain connected via the outgrowth of a thin monoepithelial cell layer, the subumbrellar plate or gastrodermal lamella.

    “At stage 4 the four radial canal tubes which at stage 3 were connected become separated by the growing bud; however, they remain connected via the outgrowth of a thin monoepithelial cell layer, the subumbrellar plate, or gastrodermal lamella”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    The daughterless heterodimer results indicate a conserved structure and dimerization function of the Podocoryne bHLH proteins.

    “indicating a conserved structure and dimerization function of the Podocoryne bHLH proteins.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.
  • May combine two claims.

    Premisecitation

    The C. elegans MyoD homologue Ce-MyoD was recently found to be functional as a homodimer and as a heterodimer with the C. elegans daughterless homologue Ce/DA.

    “However, the C. elegans MyoD homologue Ce-MyoD was recently found to be functional also as homoand heterodimer with the C. elegans daughterless homologue Ce/DA”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhang et al., 1999 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Because no signal resulted from six different primer combinations, the Id larval staining is regarded as an artifact, probably due to local most anterior gland cells.

    “However, since no signal resulted in six different primer combinations, we regard this Id staining as an artifact, probably due to the local most anterior gland cells.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    The thin smooth muscle threads running over the radial canals apparently also originate from the entocodon, although the details of their differentiation are unknown.

    “How the thin threads of smooth muscle which run on top and perpendicular to the striated muscle over the radial canals differentiate in detail (Fig. 5, colored in yellow) is not known; however, they apparently also derive from the entocodon.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationcitation

    This process places the striated and smooth muscle in an ectodermal position, which has obscured the true nature of the bell muscle.

    “This process brings the striated and smooth muscle into an ectodermal position, a situation that has helped to disguise the true character of the bell muscle (Boero et al., 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Boero et al., 1998

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    At stage 3-4, the entocodon enlarges and the endoderm pushes distally around it, forming four tubes destined to become the four radial canals.

    “At stage 3-4 (Fig. 5), the entocodon enlarges and the endoderm pushes distally around the entocodon forming four tubes destined to become the four radial canals.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Vertebrate MyoD-MyoD homodimerization occurs in vitro, and these complexes are equally stable as MyoD-E-12 heterodimers.

    “It has also been shown that vertebrate MyoD-MyoD homodimerization occurs in vitro and that these complexes are equally stable as MyoD-E-12 heterodimers.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Maleki et al., 1997

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A more detailed mutational analysis indicated that alanine and threonine are sufficient to mediate myogenic specificity, while lysine is not necessary in this context.

    “A more detailed mutational analysis has indicated that the alanine and the threonine are sufficient to mediate the myogenic specificity, while the lysine is not necessary in this context”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Davis and Weintraub, 1992

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    No other bHLH transcription factor except the myogenic activators has an alanine together with a threonine residue at those crucial positions, while alanine alone is found in many bHLH transcription factors.

    “No other bHLH transcription factor except the myogenic activators have an alanine together with a threonine residue at those crucial positions, while alanine alone is found in many bHLH transcription factors.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    Dimerization data suggest Id may partner with bHLH factors such as JellyD1 and Net-like to promote myogenesis from entocodal tissues, and may also partner with Twist in plate cells to inhibit muscle differentiation.

    “The dimerization data suggest that Id may associate with bHLH transcription factors such as JellyD1 and Net-like to promote myogenesis from entocodal tissues; however, it may also associate with Twist in the plate cells (Fig. 2B) to inhibit muscle differentiation.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Vertebrate Achaete-scute homologues have a proneural function and may also help precursors transition to differentiated cells.

    “Vertebrate Achaete-scute homologues have a proneural function and might also be involved in the transition of precursors to differentiated cells (Lee, 1997).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lee, 1997

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    JellyD1 message occurs in both developing muscle types, similar to MyoD homologues in other bilaterian invertebrates that have additional functions beyond striated muscle specification.

    “The JellyD1 message is present in both of the developing muscle types similar to MyoD homologues from other bilaterian invertebrates where the gene has other functions in addition to the specification of striated muscle (Harfe et al., 1998).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Harfe et al., 1998

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    JellyD1 expression fits a regulatory role in striated muscle determination and differentiation, and its presence in fully differentiated muscle suggests it maintains the differentiated state.

    “JellyD1 expression is consistent with a regulatory function in determination and differentiation of striated muscle cells and similar to Id and Net-like it is expressed in fully differentiated muscle, suggesting that its expression is needed for the maintenance of the differentiated state.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationcitation

    The unique Id expression pattern in medusa formation and the sequence and expression data for bHLH and other mesodermal genes support the idea that a free-living, planktonic ancestor originated the striated muscle lineage, not a sessile polyp that never forms this cell type.

    “However, the unique expression pattern of Id in medusa formation and the sequence and expression data of the bHLH and other mesodermal genes (Spring et al., 2000(Spring et al., , 2002) ) rather support the idea that a free-living, planktonic ancestor invented the striated muscle lineage and not a sessile polyp which, at least in all extant species, never differentiates this cell type.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Spring et al., 2000 source

      Not checked in the free run.

    • cites Spring et al., 2002

      Not checked in the free run.

    • Rests on an assumption: In Bilateria, striated muscle is generally derived from mesoderm, a third germ layer that Cnidaria are thought to lack.
  • May combine two claims.

    Interpretationcitation

    The medusa stage appears to have been reduced as a secondary event in the common ancestor of all extant Anthozoa, as also seen in some Hydrozoa such as Hydra.

    “Hence, it appears that the medusa stage was reduced as a secondary event in the common ancestor of all extant Anthozoa, as is seen also in some Hydrozoa such as the freshwater polyp Hydra (Schuchert, 1993;reviewed in Bouillon, 1994).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Schuchert, 1993

      Not checked in the free run.

    • cites Bouillon, 1994

      Not checked in the free run.

    • Rests on an assumption: All extant Anthozoa, such as corals and sea anemones, lack a medusa stage.
  • May combine two claims.

    Interpretationown data

    Although sequence data cannot unequivocally place JellyD1 in the MyoD family, two conserved key amino acids, the conserved interaction network, and the myogenic expression pattern indicate that Podocoryne JellyD1 corresponds to MyoD of higher animals.

    “Although sequence data do not allow us to group JellyD1 unequivocally with the MyoD family members, the two conserved crucial amino acids, the conserved interaction network, and the expression pattern during myogenesis indicate that Podocoryne JellyD1 corresponds to the MyoD of higher animals.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    Phylogenetic analysis confirms that Podocoryne Id, Ash, and Twist are true orthologues of Drosophila, mouse, and Hydra proteins, whereas Net-like and JellyD1 are more derived and cannot be grouped unequivocally.

    “The analysis confirms that Podocoryne Id, Ash, and Twist are true orthologues of proteins from Drosophila, mouse, and Hydra, while Net-like and JellyD1 are more derived and cannot be grouped unequivocally.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationcitation

    These and published data show a bilaterian-like cascade of developmentally regulated myogenic control genes in jellyfish, emphasizing the evolutionary importance of the entocodon as an ancestral, mesoderm-like structure.

    “However, these and published data demonstrate the presence of a bilaterian-like cascade of developmentally regulated myogenic control genes in jellyfish (Spring et al., 2000(Spring et al., , 2002)), which stress the evolutionary importance of the entocodon as an ancestral, mesoderm-like structure.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Spring et al., 2000 source

      Not checked in the free run.

    • cites Spring et al., 2002

      Not checked in the free run.

    • Rests on an assumption: In Bilateria, striated muscle is generally derived from mesoderm, a third germ layer that Cnidaria are thought to lack.
  • May combine two claims.

    Interpretationreasoning

    Because Id is transiently expressed in plate cells and these cells lack myofilaments, Id may inhibit myogenesis in this cell type.

    “Since Id is transiently expressed in the plate cells and since the plate cells lack myofilaments, Id may act as an inhibitor for myogenesis in this cell type.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    In Drosophila and vertebrates, Twist and Snail family members are needed for mesoderm specification and cooperate with Mef2 and MyoD family members during myogenesis.

    “In Drosophila and vertebrates, Twist (Cripps et al., 1998) and Snail (Hemavathy et al., 2000;Manazanares et al., 2001) family members are required for mesoderm specification and act together with the Mef2 and MyoD (Baylies et al., 1998) family members in myogenesis.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Cripps et al., 1998

      Not checked in the free run.

    • cites Hemavathy et al., 2000

      Not checked in the free run.

    • cites Baylies et al., 1998 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The authors propose that JellyD1 belongs to this myogenic cascade and acts downstream of Twist and Snail during muscle differentiation.

    “We propose JellyD1 to be a member of this cascade and a downstream target of Twist and Snail in the muscle differentiation process.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Premisecitation

    In Drosophila and vertebrates, Id binds other transcription factors and inhibits muscle differentiation.

    “In Drosophila (Cubas et al., 1994) and vertebrates (Jen et al., 1997) Id associates with other transcription factors to inhibit muscle differentiation.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cubas et al., 1994

      Not checked in the free run.

    • cites Jen et al., 1997

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In Drosophila, achaete-scute complex members are proneural proteins involved in external sensory organ formation.

    “In Drosophila, members of the achaete-scute complex are proneural proteins and are involved in external sensory organ formation (Jan and Jan, 1993).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jan and Jan, 1993

      Not checked in the free run.

80 of 80
  • The paper relies on this without support.

    Striated muscle tissue first appears in jellyfish, and the question of its evolutionary position is controversially discussed.

    “In phylogeny striated muscle tissue appears first in jellyfish and the question of its evolutionary position is controversially discussed.”
  • The authors state this as an assumption.

    The strength of reporter gene activation, as measured by lacZ activity, reflects the strength of the protein-protein interactions.

    “The strength of reporter gene activation, as measured by lacZ activity, is assumed to reflect the strength of the protein-protein interactions.”
  • The authors state this as an assumption.

    Ash could be involved in nematocyte differentiation in larvae.

    “we assume that it could be involved in nematocyte differentiation in larvae.”
  • The paper relies on this without support.

    All extant Anthozoa, such as corals and sea anemones, lack a medusa stage.

    “Because extant Anthozoa such as corals or sea anemones all lack a medusa stage, it was assumed that the medusa evolved later.”
  • The paper relies on this without support.

    In Bilateria, striated muscle is generally derived from mesoderm, a third germ layer that Cnidaria are thought to lack.

    “In Bilateria this cell type in general is a derivative of the mesoderm, a third germ layer that is supposedly missing in Cnidaria.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Cnidarian homologs of bilaterian mesoderm and myogenic regulators are expressed in larval and polyp stages and in the entocodon and its derived striated muscle.

    “According to recent molecular studies cnidarian homologs to bilaterian mesoderm and myogenic regulators are expressed in the larval and polyp stages as well as in the entocodon and derived striated muscle.”

    From Evolution of striated muscle: Jellyfish and the origin of triploblasty (2005) · cites this paper as Müller et al., 2003

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 4 panel Ash c is assigned to two different specimens

    Minor

    The text identifies panel Ash c as a planula larva showing endodermal staining, while the figure caption identifies it as a medusa tentacle bulb.

  • Ash clone extends beyond the stated protein length

    Minor

    Ash is described as a 158-amino-acid protein, but the stated Ash fusion construct includes residue 159.

  • Net-like clone extends beyond the stated protein length

    Minor

    Net-like is described as a 148-amino-acid protein, but the stated Net fusion construct includes residue 149.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 15

  1. Altschul, 1997, Gapped BLAST and PSI-BLAST, Nucleic Acids Res., 25, 3389, 10.1093/nar/25.17.3389 · DOI · Paper page
  2. Baylies, 1998, Myogenesis, Cell, 93, 921, 10.1016/S0092-8674(00)81198-8 · DOI · Paper page
  3. Baylies, 2001, Invertebrate myogenesis, Curr. Opin. Genet. Dev., 11, 431, 10.1016/S0959-437X(00)00214-8 · DOI
  4. Brentrup, 2000, Regulation of Drosophila wing vein patterning, Development, 127, 4729, 10.1242/dev.127.21.4729 · DOI
  5. Bridge, 1995, Class-level relationships in the phylum Cnidaria, Mol. Biol. Evol., 12, 679
  6. Grens, 1995, Evolutionary conservation of a cell fate specification gene, Development, 121, 4027, 10.1242/dev.121.12.4027 · DOI · Paper page
  7. Gröger, 2001, Larval development in Cnidaria, Genesis, 29, 110, 10.1002/gene.1013 · DOI
  8. Hemavathy, 2000, Snail/Slug family of repressors, Gene, 257, 1, 10.1016/S0378-1119(00)00371-1 · DOI
  9. Hollenberg, 1995, Identification of a new family of tissue-specific basic Helix-Loop-Helix transcription factors with a two-hybrid system, Mol. Cell. Biol., 7, 3818
  10. Jen, 1997, Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis, Dev. Dyn., 208, 92, 10.1002/(SICI)1097-0177(199701)208:1<92::AID-AJA9>3.0.CO;2-X · DOI
  11. Kühn, 1910, Die Entwicklunsgeschichte der Geschlechtsindividuen der Hydromedusen, Zool. Jahrb. Abt. Syst. Ockol. Geogr. Tiere, 30, 145
  12. Massari, 2000, Helix-loop-helix proteins, Mol. Cell. Biol., 20, 429, 10.1128/MCB.20.2.429-440.2000 · DOI
  13. Schuchert, 1993, Phylogenetic analysis of the Cnidaria, Z. Zool. Syst. Evol., 31, 161, 10.1111/j.1439-0469.1993.tb00187.x · DOI
  14. Spring, 2002, Conservation of Brachyury, Mef2, and Snail in the myogenic lineage of jellyfish, Dev. Biol., 244, 372, 10.1006/dbio.2002.0616 · DOI · Paper page
  15. Weintraub, 1993, The MyoD family and myogenesis, Cell, 75, 1241, 10.1016/0092-8674(93)90610-3 · DOI · Paper page

Cited by

Sorted by citations

Authors
Müller, P., Seipel, K., Yanze, N., Reber-Müller, S., Streitwolf-Engel, R., Stierwald, M., Spring, J. Ü., & Schmid, V.
Affiliations
University of Basel (CH)
Corresponding author
Schmid, Volker
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2003-03
Volume
255
Issue
2
Pages
216-229
ISSN
0012-1606 (ISSN-L)
OpenAlex
W1980517461
Cited by
69
References
47
Citations by year
2023: 1 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 3
FWCI
10.66
Type
journal article
Language
en
Open access
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • Stiftung für die Erforschung der Muskelkrankheiten
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Physical Sciences › Earth and Planetary Sciences › Paleontology › Marine Invertebrate Physiology and Ecology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
bHLH transcription factors, jellyfish, Podocoryne carnea, medusa development, MyoD, id, ash, mesoderm origin, Cnidaria, Bilateria, planula larvae, gene expression patterns
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, Molecular Sequence Data, Repressor Proteins, Transcription Factors, Sequence Homology, Amino Acid, In Situ Hybridization, DNA, Complementary, Helix-Loop-Helix Motifs, Muscle, Skeletal, Gene Expression Regulation, Developmental, Evolution, Molecular, Hydrozoa, Inhibitor of Differentiation Protein 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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