CoChat
Sign Up
Cited by 84Marine Invertebrate Physiology and EcologyDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

Evolution of eumetazoan nervous systems: insights from cnidarians

Open access
Kelava, Iva, Rentzsch, Fabian, Technau, Ulrich·2015·Philosophical Transactions of the Royal Society B: Biological Sciences
DOI 10.1098/rstb.2015.0065PMC PMC4650132
Open this paper in CoChat — free accountOpen PDF

Abstract

Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system—in particular the nervous system of the anthozoan Nematostella vectensis . It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, and Sox genes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes evidence on cnidarian nervous system evolution, focusing on the anthozoan model *Nematostella vectensis*. It concludes that key neurogenic genes and pathways are partly conserved between cnidarians and bilaterians, while cnidarians also show distinct features such as endodermal neurogenesis and independently evolved neuronal ion-channel properties.

Key findings

  • *Nematostella* has interconnected ectodermal and endodermal neuronal networks with sensory cells, ganglion cells, and cnidocytes; neuronal subpopulations are marked by Elav1, SoxB(2), RFamide, GLWamide, and GABA. GLWamide-positive neurons appear at 2–3 days post fertilization (dpf), and at 4 dpf RFamide/GLWamide subpopulations make up around 8% of Elav1-positive neurons, though Elav1 is not a pan-neuronal marker.
  • Neurogenesis begins at mid-to-late blastula in an aboral territory spanning approximately 75% of body length; the oral cap is initially devoid of differentiating neurons, and the apical organ remains free of Elav1 and SoxB(2) neural cell bodies. Later neurons are born orally and in the endoderm.
  • Conserved molecular components include Wnt/β-catenin, BMP, SoxB(2), Notch/Delta, and bHLH proneural genes. β-catenin inhibition severely reduces RFamide, GLWamide, and Elav1::mOrange neurons, while ectopic activation increases them; BMP has no early effect but a proneural later role; SoxB(2) marks a neural progenitor population giving rise to ganglion/sensory neurons and cnidocytes, and its knockdown strongly reduces both.
  • The authors conclude the last common ancestor of Bilateria and Cnidaria had a well-established nervous system with neurons born from epithelial cells singled out by a Notch/Delta-like mechanism. Differences include the puzzle of endodermal neurogenesis, cnidocytes as part of the neuronal lineage, and independent evolution of voltage-gated Na+ channel selectivity filters in cnidarians and bilaterians.

Methods

  • This is a review/synthesis, not a primary experimental study; it discusses cnidarian nervous systems with emphasis on recent findings in *Nematostella vectensis* and compares them with bilaterians.
  • It draws on cited studies using genome sequencing/bioinformatics, gene knockdown, transgenic reporter lines (e.g., Elav1::mOrange, SoxB(2)::mOrange), pharmacological treatments (DAPT, β-catenin inhibitor/activation), immunostaining for neuropeptides and GABA, transplantation, and EdU labeling.
  • The main analysis is comparative evolutionary developmental interpretation across cnidarian taxa (Anthozoa, Medusozoa, *Hydra*, *Clytia*, *Hydractinia*, *Aurelia*) and bilaterians.

Limitations

  • The paper states that no pan-neuronal marker is available, antibodies are limited, and double/triple stainings are lacking, making it difficult to determine which fraction of neurons express two or more neuropeptides; it also notes discrepancies between bioinformatic and empirical data, such as serotonin.
  • The paper states that the full regulatory network remains to be elucidated and that many questions remain about the molecular signature of cnidarian neural progenitors and neurons, cellular processes, and nervous system physiology/homeostasis.
  • Evident from the text: as a review, it presents no new primary data and no systematic review methodology; some conclusions rely on cited studies, including unpublished data (I.K. and U.T. 2015, unpublished data), and unresolved non-bilaterian phylogeny affects evolutionary scenarios.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1098/rstb.2015.0065

Cites

82 of 82 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 95 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Two smaller neuronal subpopulations expressing RFamide and GLWamide are primarily found in the oral half of the young polyp.

    “Two smaller neuronal subpopulations expressing specific neuropeptides, RFamide and GLWamide [30,31], are primarily found in the oral half of the young polyp.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [30] Schmich J, Rudolf R, Trepel S, Leitz T 1998 Immunohistochemical studies of GLWamides in Cnidaria. Cell Tissue Res. 294, 169– 177. (10.1007/s004410051167) 9724467 source

      Not checked in the free run.

    • cites [31] Takahashi T, Hatta M 2011 The importance of GLWamide neuropeptides in cnidarian development and physiology. J. Amino Acids 2011, 424501 (10.4061/2011/424501) 22312460 PMC3268022 source

      Not checked in the free run.

  • Findingown data

    Elav1-positive neurons form networks both in the ectoderm and in the endoderm.

    “Elav1-positive neurons form networks both in the ectoderm and in the endoderm (figure 2a,d).”
    Quote in the paperNot a substantial claim
  • Findingcitation

    In the endoderm, many neurons follow the parietal muscles on either side of the eight mesenteries, forming prominent longitudinal tracts.

    “In the endoderm, however, many neurons follow the parietal muscles on either side of the eight mesenteries, forming prominent longitudinal tracts [27].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Nakanishi N, Renfer E, Technau U, Rentzsch F 2012 Nervous systems of the sea anemone Nematostella vectensis are generated by ectoderm and endoderm and shaped by distinct mechanisms. Development 139, 347– 357. (10.1242/dev.071902) 22159579 source

      Not checked in the free run.

  • Findingcitation

    The expression patterns of candidate guidance molecules such as Netrin or RGM do not obviously relate to the observed changes in neurite projections of Elav1-positive neurons.

    “In fact, the expression patterns of candidate guidance molecules, such as Netrin or RGM, do not obviously relate to the observed changes in neurite projections of Elav1-positive neurons [24,39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [24] Magie CR, Pang K, Martindale MQ 2005 Genomic inventory and expression of Sox and Fox genes in the cnidarian Nematostella vectensis. Dev. Genes Evol. 215, 618– 630. (10.1007/s00427-005-0022-y) 16193320 source

      Not checked in the free run.

    • cites [39] Leclère L, Rentzsch F 2014 RGM regulates BMP-mediated secondary axis formation in the sea anemone Nematostella vectensis. Cell Rep. 9, 1921– 1930. (10.1016/j.celrep.2014.11.009) 25482565 source

      Not checked in the free run.

  • Findingcitation

    The asymmetric distribution of early GLWamide-positive neurons, together with the RFamide-positive population, depends on BMP signalling along the directive axis.

    “Interestingly, the previously mentioned asymmetric distribution of early GLWamide-positive neurons (see above), together with the RFamide-positive population, depends on BMP signalling along the directive axis [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims. 28
  • Classified as probably not a substantial claim. 5
  • The quote only partly states this claim. 1
  • Not yet classified. 1

  • May combine two claims.

    Findingcitation

    GLWamide-positive neurons appear 2-3 days post fertilization and initially appear on one side of the developing pharynx in the planula.

    “This population appears 2–3 days post fertilization (dpf), but, unlike the RFamide-positive neurons, the GLWamide-positive neurons initially appear on the one side of the developing pharynx in the planula [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In the polyp of Nematostella vectensis, neuron density appears higher in the oral half, but previous suggestions of an oral nerve ring could not be confirmed.

    “In the polyp, N. vectensis, the neuron density appears to be higher in the oral half of the animal, but previous suggestions of an oral nerve ring [26] could not be confirmed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Marlow HQ, Srivastava M, Matus DQ, Rokhsar D, Martindale MQ 2009 Anatomy and development of the nervous system of Nematostella vectensis, an anthozoan cnidarian. Dev. Neurobiol. 69, 235– 254. (10.1002/dneu.20698) 19170043

      Not checked in the free run.

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

    Findingcitation

    At 4 days post fertilization, RFamide and GLWamide subpopulations make up around 8% of the Elav1-positive neurons.

    “It has been reported that at 4 dpf these subpopulations make up around 8% of the Elav1-positive neurons [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    GABA-neurons do not appear to form connections to each other and seem embedded as individual neurons in the nervous system.

    “Interestingly, the GABA-neurons do not appear to form connections to each other and seem embedded as individual neurons in the nervous system, raising questions about their role.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Elav1::mOrange-positive sensory cells predominantly project in an aboral direction at early- and mid-planula stage, while later-born Elav1 neurons preferentially project in transverse orientation.

    “Interestingly, Elav1::mOrange-positive sensory cells, which constitute a subset of the SoxB(2)::mOrange cells, predominantly project in an aboral direction at early- and mid-planula stage. Later-born Elav1 neurons, however, preferentially project in transverse orientation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The BMP signalling gradient in Nematostella has been detected only considerably later (at gastrula stage) than the occurrence of the first neural progenitor cells (at mid-blastula stage), and early neural differentiation is not biased along the directive axis.

    “However, this BMP signalling gradient has been detected only considerably later (at gastrula stage, [39,40]) than the occurrence of the first neural progenitor cells (NPCs; at mid-blastula stage [29]) and early neural differentiation is not biased along the directive axis [26,27,29,41].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [39] Leclère L, Rentzsch F 2014 RGM regulates BMP-mediated secondary axis formation in the sea anemone Nematostella vectensis. Cell Rep. 9, 1921– 1930. (10.1016/j.celrep.2014.11.009) 25482565

      Not checked in the free run.

    • cites [40] Genikhovich G et al. 2015 Axis patterning by BMPs: cnidarian network reveals evolutionary constraints. Cell Rep. 10, 1646– 1654. (10.1016/j.celrep.2015.02.035) PMC4460265 25772352

      Not checked in the free run.

    • cites [29] Richards GS, Rentzsch F 2014 Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis. Development 141, 4681– 4689. (10.1242/dev.112029) 25395455 source

      Not checked in the free run.

    • cites [26] Marlow HQ, Srivastava M, Matus DQ, Rokhsar D, Martindale MQ 2009 Anatomy and development of the nervous system of Nematostella vectensis, an anthozoan cnidarian. Dev. Neurobiol. 69, 235– 254. (10.1002/dneu.20698) 19170043

      Not checked in the free run.

    • cites [27] Nakanishi N, Renfer E, Technau U, Rentzsch F 2012 Nervous systems of the sea anemone Nematostella vectensis are generated by ectoderm and endoderm and shaped by distinct mechanisms. Development 139, 347– 357. (10.1242/dev.071902) 22159579

      Not checked in the free run.

    • cites [41] Layden MJ, Boekhout M, Martindale MQ 2012 Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway. Development 139, 1013– 1022. (10.1242/dev.073221) 22318631 PMC3274362

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    six3/6, FoxQ2a and irx are expressed at the aboral end of the Nematostella planula, suggesting conservation of regional patterning genes.

    “Strikingly, six3/6, FoxQ2a and irx are actually expressed at the aboral end of the Nematostella planula [54], suggesting a stunning conservation of regional patterning genes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Sinigaglia C, Busengdal H, Leclère L, Technau U, Rentzsch F 2013 The bilaterian head patterning gene six3/6 controls aboral domain development in a cnidarian. PLoS Biol. 11, e1001488 (10.1371/journal.pbio.1001488) 23483856 PMC3586664

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    Knockdown of Nematostella six3/6 reduced the number of DmrtB-expressing aboral neurons but did not affect expression of the broader neural marker RFamide, suggesting the effect on aboral neurons is a consequence of mis-specification of the aboral domain.

    “Knockdown of Nematostella six3/6 reduced the number of DmrtB-expressing aboral neurons, but did not affect the expression of the broader neural marker RFamide, suggesting that the effect on the aboral neurons is rather a consequence of the mis-specification of the aboral domain.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In Nematostella, BMP signalling appears to have no effect on neuronal differentiation at an early phase, but a proneural function in the later phase of embryonic neurogenesis.

    “in Nematostella, BMP signalling appears to have no effect on neuronal differentiation at an early phase, but a proneural function in the later phase of embryonic neurogenesis [28].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    One ato gene, Arp6, is expressed asymmetrically in the developing embryo, and functional analysis suggests it regulates the asymmetric distribution of GLWamide-positive neurons.

    “Interestingly, one of the ato genes, Arp6, is expressed asymmetrically in the developing embryo and functional analysis suggests that it regulates the asymmetric distribution of GLWamide-positive neurons.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In Nematostella, the Notch/Delta system is involved in determining the fate of neural lineage cells, and Notch/Delta signalling influences the expression of neurogenic markers such as AshA.

    “It appears that, in Nematostella, the Notch/Delta system is also involved in determining the fate of neural lineage cells. By using pharmacological treatments with the γ-secretase inhibitor DAPT, it was shown that the Notch/Delta signalling influences the expression of neurogenic markers [60], e.g. the achaete-scute homologue (AshA) among others [61].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [60] Marlow H, Roettinger E, Boekhout M, Martindale MQ 2012 Functional roles of Notch signaling in the cnidarian Nematostella vectensis. Dev. Biol. 362, 295– 308. (10.1016/j.ydbio.2011.11.012) 22155407 PMC3771581

      Not checked in the free run.

    • cites [61] Layden MJ, Martindale MQ 2014 Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation. EvoDevo. 5, 30 (10.1186/2041-9139-5-30) 25705370 PMC4335385 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    GABA marks a population of neurons present only in the endoderm, with a tendency to be more concentrated in the aboral region.

    “Recently, we discovered that the neurotransmitter gamma amino butyric acid (GABA) marks a population of neurons that is present only in the endoderm, with the tendency to be more concentrated in the aboral region (figure 2d,e; I.K. and U.T. 2015, unpublished data).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Use of a β-catenin signalling inhibitor severely reduced RFamide, GLWamide and Elav1::mOrange neurons at planula stage, whereas ectopic activation of β-catenin increased the number of these neurons.

    “Use of a β-catenin signalling inhibitor resulted in a severe reduction of RFamide, GLWamide and Elav1::mOrange neurons at planula stage, whereas ectopic activation of β-catenin increased the number of these neurons [28].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    At early gastrulation, the oral cap is devoid of differentiating neurons, whereas after gastrulation, more neurons-including RFamide and GLWamide neurons-are born in the oral half and in the endoderm.

    “At early gastrulation, the oral cap is devoid of differentiating neurons, whereas after gastrulation, more neurons—including some specific subpopulations (RFamide, GLWamide neurons)—are born in the oral half (in and around the pharynx) and in the endoderm [26–28] (figure 3b).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [26] Marlow HQ, Srivastava M, Matus DQ, Rokhsar D, Martindale MQ 2009 Anatomy and development of the nervous system of Nematostella vectensis, an anthozoan cnidarian. Dev. Neurobiol. 69, 235– 254. (10.1002/dneu.20698) 19170043

      Not checked in the free run.

    • cites [27] Nakanishi N, Renfer E, Technau U, Rentzsch F 2012 Nervous systems of the sea anemone Nematostella vectensis are generated by ectoderm and endoderm and shaped by distinct mechanisms. Development 139, 347– 357. (10.1242/dev.071902) 22159579

      Not checked in the free run.

    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Manipulation of the Wnt pathway affects the development of oral RFamide and Elav1 neurons, suggesting a conserved role for Wnt signalling in promoting neurogenesis.

    “However, in contrast to this idea, recent work showed that manipulation of the Wnt pathway affects the development of oral RFamide and Elav1 neurons [28], suggesting a conserved role for Wnt signalling in promoting neurogenesis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    AshA is expressed in single cells of the aboral half of the early embryo and is directly involved in neurogenesis: knockdown leads to loss of specific neuronal markers, and overexpression increases the number of RFamide+ and Elav1-precursor cells in the aboral half.

    “At least one, AshA, is expressed in single cells of the aboral half of the early embryo and is directly involved in neurogenesis: knockdown leads to loss of specific neuronal markers, overexpression increases the number of RFamide+ and Elav1-precursor cells in the aboral half [41].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Layden MJ, Boekhout M, Martindale MQ 2012 Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway. Development 139, 1013– 1022. (10.1242/dev.073221) 22318631 PMC3274362

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    RFamide and GLWamide are found in all cnidarians and many bilaterians examined so far.

    “Both of them are found in all cnidarians and many bilaterians examined so far [26,28,32–34]”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [26] Marlow HQ, Srivastava M, Matus DQ, Rokhsar D, Martindale MQ 2009 Anatomy and development of the nervous system of Nematostella vectensis, an anthozoan cnidarian. Dev. Neurobiol. 69, 235– 254. (10.1002/dneu.20698) 19170043

      Not checked in the free run.

    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

    • cites [32] Grimmelikhuijzen C, Leviev I, Carstensen K 1996 Peptides in the nervous systems of cnidarians: structure, function, and biosynthesis. Int. Rev. Cytol. 167, 37– 89. (10.1016/S0074-7696(08)61345-5) 8768492

      Not checked in the free run.

    • cites [33] Grimmelikhuijzen C, Williamson M, Hansen G 2002 Neuropeptides in cnidarians. Can. J. Zool. 80, 1690– 1702. (10.1139/z02-137)

      Not checked in the free run.

    • cites [34] Jékely G 2013 Global view of the evolution and diversity of metazoan neuropeptide signaling. Proc. Natl Acad. Sci. USA 110, 8702– 8707. (10.1073/pnas.1221833110) 23637342 PMC3666674

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Cnidaria and comparison with Bilateria are crucial for reconstructing a cnidarian-bilaterian ancestor and for understanding the evolution of eumetazoan nervous systems.

    “Hence, the Cnidaria and the comparison with Bilateria are crucial for the reconstruction of a cnidarian–bilaterian ancestor and our understanding of the evolution of eumetazoan nervous systems.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Nematostella vectensis has a surprisingly complex genome, including all major signalling pathways and most transcription factor families.

    “Nematostella has a surprisingly complex genome, including all major signalling pathways and most transcription factor families [18,20–24].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [18] Rentzsch F, Fritzenwanker JH, Scholz CB, Technau U 2008 FGF signalling controls formation of the apical sensory organ in the cnidarian Nematostella vectensis. Development 135, 1761– 1769. (10.1242/dev.020784) 18441276

      Not checked in the free run.

    • cites [20] Technau U et al. 2005 Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. Trends Genet. 21, 633– 639. (10.1016/j.tig.2005.09.007) 16226338 source

      Not checked in the free run.

    • cites [21] Saina M, Genikhovich G, Renfer E, Technau U 2009 BMPs and chordin regulate patterning of the directive axis in a sea anemone. Proc. Natl Acad. Sci. USA 106, 18 592– 18 597. (10.1073/pnas.0900151106) 19833871 PMC2773963

      Not checked in the free run.

    • cites [22] Matus DQ, Magie CR, Pang K, Martindale MQ, Thomsen GH 2008 The Hedgehog gene family of the cnidarian, Nematostella vectensis, and implications for understanding metazoan Hedgehog pathway evolution. Dev. Biol. 313, 501– 518. (10.1016/j.ydbio.2007.09.032) 18068698 PMC2288667

      Not checked in the free run.

    • cites [23] Matus DQ, Pang K, Daly M, Martindale MQ 2007 Expression of Pax gene family members in the anthozoan cnidarian, Nematostella vectensis. Evol. Dev. 9, 25– 38. (10.1111/j.1525-142X.2006.00135.x) 17227364

      Not checked in the free run.

    • cites [24] Magie CR, Pang K, Martindale MQ 2005 Genomic inventory and expression of Sox and Fox genes in the cnidarian Nematostella vectensis. Dev. Genes Evol. 215, 618– 630. (10.1007/s00427-005-0022-y) 16193320

      Not checked in the free run.

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

    Premisecitation

    Cnidarians are divided into Anthozoa (Hexacorallia and Octocorallia) and Medusozoa (Hydrozoa, Scyphozoa, Cubozoa and Staurozoa).

    “The cnidarians are divided into two major groups, the Anthozoa, consisting of Hexacorallia and Octocorallia, and the Medusozoa, which comprise Hydrozoa, Scyphozoa, Cubozoa and Staurozoa (figure 1a; [9]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Collins AG, Schuchert P, Marques AC, Jankowski T, Medina M, Schierwater B 2006 Medusozoan phylogeny and character evolution clarified by new large and small subunit rDNA data and an assessment of the utility of phylogenetic mixture models. Syst. Biol. 55, 97– 115. (10.1080/10635150500433615) 16507527

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Nematostella, Elav1 marks a large neuronal subpopulation but is not a pan-neuronal marker, because it is part of a larger population marked by SoxB(2).

    “In Nematostella, it indeed marks a large neuronal subpopulation [26,27], but is not a pan-neuronal marker (figure 2a,e), as it is part of a larger population marked by SoxB(2) [29]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [26] Marlow HQ, Srivastava M, Matus DQ, Rokhsar D, Martindale MQ 2009 Anatomy and development of the nervous system of Nematostella vectensis, an anthozoan cnidarian. Dev. Neurobiol. 69, 235– 254. (10.1002/dneu.20698) 19170043

      Not checked in the free run.

    • cites [27] Nakanishi N, Renfer E, Technau U, Rentzsch F 2012 Nervous systems of the sea anemone Nematostella vectensis are generated by ectoderm and endoderm and shaped by distinct mechanisms. Development 139, 347– 357. (10.1242/dev.071902) 22159579

      Not checked in the free run.

    • cites [29] Richards GS, Rentzsch F 2014 Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis. Development 141, 4681– 4689. (10.1242/dev.112029) 25395455 source

      Not checked in the free run.

  • The quote only partly states this claim.

    Interpretationreasoning

    The development of the nervous system in Nematostella displays striking differences from that in Hydra and other hydrozoans such as Clytia hemisphaerica and Hydractinia echinata.

    “The development of the nervous system in Nematostella displays some striking differences to that in Hydra and other hydrozoans such as Clytia hemisphaerica and Hydractinia echinata.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    SoxB(2) marks a population of cells that gives rise to ganglion and sensory neurons and cnidocytes, representing a general neural progenitor population.

    “Using a SoxB(2) transgenic reporter line, Richards and Rentzsch showed that SoxB(2) marks a population of cells that gives rise to ganglion and sensory neurons and cnidocytes, thus representing a general neural progenitor population [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Richards GS, Rentzsch F 2014 Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis. Development 141, 4681– 4689. (10.1242/dev.112029) 25395455 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Hydra, RFamide marks mostly ectodermal sensory neurons of the hypostome and tentacles, but also ectodermal ganglion neurons of the peduncle, which might have a propriosensory function because ultrastructural studies showed cilia.

    “in Hydra, RFamide marks mostly ectodermal sensory neurons of the hypostome and tentacles, but also ectodermal ganglion neurons of the peduncle, although they might also have at least a propriosensory function, because ultrastructural studies showed that they contain cilia [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Westfall JA 1973 Ultrastructural evidence for a granule-containing sensory-motor-interneuron in Hydra littoralis. J. Ultrastruct. Res. 42, 268– 282. (10.1016/S0022-5320(73)90055-5) 4702922

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    i-cells have only been found in hydrozoans and are considered a specific feature of hydrozoans.

    “However, i-cells have only been found in hydrozoans and therefore are considered a specific feature of hydrozoans.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Pax6 and Sox2 are markers of intermediate progenitors in the developing mammalian brain.

    “Pax6 and Sox2 are markers of these intermediate progenitors in the developing mammalian brain [58].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Paridaen JTML, Huttner WB 2014 Neurogenesis during development of the vertebrate central nervous system. EMBO Rep. 15, 351– 364. (10.1002/embr.201438447) 24639559 PMC3989667

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The confined expression of individual neuronal markers reveals a hidden complexity of the Nematostella nervous system, with neuronal subpopulations that might be dedicated to different processes and/or behaviours.

    “The confined expression of individual neuronal markers reveals a hidden complexity of the Nematostella nervous system, with neuronal subpopulations that might be dedicated to different processes and/or behaviours.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Sox proteins are indispensable in the determination and maintenance of embryonic stem cells in mammals, and later, during brain development, in the population of neural progenitor cells.

    “Sox proteins are indispensable in the determination and maintenance of embryonic stem cells in mammals, and later, during brain development, in the population of NPCs [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Guth SIE, Wegner M 2008 Having it both ways: Sox protein function between conservation and innovation. Cell Mol. Life Sci. 65, 3000– 3018. (10.1007/s00018-008-8138-7) 18516494 PMC11131603

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Cnidocytes are part of the neuronal lineage and stem from the same progenitor pool as neurons.

    “The cnidocyte, the cnidarian-specific cell type, is also a part of the neuronal lineage, as it seems that it stems from the same progenitor pool.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Members of the Sox family of genes are involved in the patterning of the neural field and the production of the components of the neural lineage.

    “It has been shown that members of the Sox family of genes are involved in the patterning of the neural field and the production of the components of the neural lineage [28,29].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

    • cites [29] Richards GS, Rentzsch F 2014 Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis. Development 141, 4681– 4689. (10.1242/dev.112029) 25395455 source

      Not checked in the free run.

  • Not yet classified.

    Premise

    Another SoxB2 gene is involved in patterning the oral nervous system.

    “In addition to SoxB(2), as mentioned above, another SoxB2 gene is involved in patterning the oral nervous system [28].”
    Quote in the paperNot yet classified0 of 1 sources checked
    • cites [28] Watanabe H, Kuhn A, Fushiki M, Agata K, Özbek S, Fujisawa T, Holstein TW 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis. Nat. Commun. 5, 5536 (10.1038/ncomms6536) 25534229 PMC4284808 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nematostella PaxA and PaxB are expressed in single cells, reminiscent of a pattern present in progenitors and/or neurons.

    “In line with this, Nematostella PaxA and PaxB are expressed in single cells, reminiscent of a pattern present in progenitors and/or neurons [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Magie CR, Pang K, Martindale MQ 2005 Genomic inventory and expression of Sox and Fox genes in the cnidarian Nematostella vectensis. Dev. Genes Evol. 215, 618– 630. (10.1007/s00427-005-0022-y) 16193320

      Not checked in the free run.

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

    Premisecitation

    Cnidocytes express one of the three subfamilies of the EAG family of voltage-gated K+ channels.

    “Interestingly, cnidocytes express one of the three subfamilies of the ether-à-go-go (EAG) family of voltage-gated K+ channels [79].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [79] Li X, Martinson AS, Layden MJ, Diatta FH, Sberna AP, Simmons DK, Martindale MQ, Jegla TJ 2015 Ether-à-go-go family voltage-gated K+ channels evolved in an ancestral metazoan and functionally diversified in a cnidarian–bilaterian ancestor. J. Exp. Biol. 218, 526– 536. (10.1242/jeb.110080) 25696816 PMC4334144 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These epithelial cells most probably underwent an asymmetric division, to produce a differentiated neuron and presumably another epithelial cell or a neural progenitor.

    “These epithelial cells most probably underwent an asymmetric division, to produce a differentiated cell—a neuron, and presumably another epithelial cell or a neural progenitor.”
    Quote in the paperNot a substantial claim
34 of 34

  • The paper relies on this without support.

    The nervous system is a defining characteristic of Metazoa, except in Placozoa and Porifera.

    “With the exception of Placozoa and Porifera, the nervous system is a defining characteristic of Metazoa”

  • The paper relies on this without support.

    Comparing the cnidarian developmental programme with the bilaterian developmental programme can reveal genes and processes involved in the development of ancestral nervous systems.

    “by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems.”
2 of 2

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?

  • At least 600 million years of evolution separate cnidarians from bilaterians.

    “Though at least 600 million years of evolution separate cnidarians from bilaterians [9–16], many aspects of the nervous system are conserved, including neuropeptides and neurotransmitters [15–20].”

    From The Jellyfish Cassiopea Exhibits a Sleep-like State (2017) · cites this paper as [14]

  • Cnidarians include jellyfishes and polyps, are distinguished by nematocysts, and have long been used as laboratory experimental organisms.

    “Cnidarians, which include jellyfishes and polyps and are distinguished by their nematocysts (stinging cells), have long been utilized in laboratories as experimental organisms to address diverse biological questions [16–20].”

    From Back to the Basics: Cnidarians Start to Fire (2017) · cites this paper as [18]

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 2d is cited for Elav1 neurons but depicts GABA neurons

    Minor

    The text cites figure 2d for Elav1-positive neuronal networks, but the figure caption identifies panel 2d as showing GABA-positive neurons.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Technau U, 2015, Evolutionary developmental biology of invertebrates

Cited by

Sorted by citations

Authors
Kelava, I., Rentzsch, F., & Technau, U.
Affiliations
  • University of Vienna (AT)
  • Sars Centre, Sars International Centre for Marine Molecular Biology, Thormøhlensgt. 55, 5008 Bergen, Norway
Corresponding author
Technau, Ulrich
ORCID
Venue
Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher
The Royal Society
Published
2015-12-19
Volume
370
Issue
1684
Pages
20150065
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
DOI
10.1098/rstb.2015.0065
PMC
PMC4650132
OpenAlex
W2210542807
Semantic Scholar
d6805484ac9b50ec05e6eb5c9eea2283f6744d5c
Cited by
84
References
82
Citations by year
2026: 8 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 11 · 2018: 8 · 2017: 9 · 2016: 8 · 2015: 1
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
Austrian Science Fund (M1680)
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 › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
nervous system evolution, Cnidaria, Nematostella vectensis, Anthozoa, neurogenesis, neuronal differentiation, Wnt signaling, BMP signaling, Sox genes, gene regulatory networks, bilaterian evolution, non-model organisms
MeSH terms
Animals, Cnidaria, Biological Evolution, Gene Expression Regulation, Nervous System

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review