Back to the Basics: Cnidarians Start to Fire

Probably not a substantial claim: may not pass S4 (based).

Recent advances in molecular and imaging methods are fueling renewed interest and research into cnidarian nervous systems.

“recent advances in molecular and imaging methods are fueling a renaissance of interest in and research into cnidarians nervous systems”

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

Comparative approaches have been central to neuroscience since Cajal.

“Since the time of Cajal, comparative approaches have been central to neuroscience [1].”

• cites [1] Cajal SR 1906 In Nobel lectures, physiology or medicine 1901–1921Not checked yet

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Comparative work enabled the earlier discovery of dendritic spines in chicken.

“the earlier discovery of dendritic spines (chicken) [8]”

• cites [8] Cajal SR 1888 Estructura de los centros nerviosos de las avesNot checked yet

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Aplysia was used to elucidate mechanisms of habituation, sensitization, and associative learning.

“the marine mollusc Aplysia californica, to elucidate mechanisms of neural function that specifically mediate habituation, sensitization, and forms of associative learning [4]”

• cites [4] Kandel E Schwartz J 2013 Principles of Neural Science, Fifth Edition McGraw-Hill EducationNot checked yet

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Optogenetic temporal control of neuronal function advanced through characterization of channelrhodopsins in algae.

“significant advancements in temporal control of neuronal function through optogenetics have been made thanks to the characterization of channel-rhodopsins in algae [9]”

• cites [9] Nagel G 2003 Channelrhodopsin-2, a directly light-gated cation-selective membrane channel Proc Natl Acad Sci 100 13940 13945 14615590 PMC283525Not checked yet

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Cnidarian nervous systems have great potential to inform basic structural and functional principles of neural circuits.

“have great potential to inform us about basic structural and functional principles of neural circuits”

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

Comparative work enabled the discovery of conditioned reflexes in dog.

“conditioned reflexes (dog) [7]”

• cites [7] Pavlov IP 1951 Conditioned reflex Feldsher Akush 10 3 10 14887723Not checked yet

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Comparative work enabled the discovery of the ionic basis of the action potential in squid.

“the understanding of the ionic basis of the action potential (squid) [5]”

• cites [5] Hodgkin AL Huxley AF 1952 The components of membrane conductance in the giant axon of Loligo J Physiol 116 473 496 14946714 PMC1392209Not checked yet

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Modern neuroscience focuses on entire neural circuits as the unit responsible for emergent functional properties.

“modern neuroscience is now focused on understanding entire neural circuits, as they may be the unit responsible for emergent functional properties [3]”

• cites [3] Yuste R 2015 From the neuron doctrine to neural networks Nat Rev Neurosci 16 487 497 26152865Not checked yet

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The neuron doctrine established the individual neuron as the functional unit of the nervous system.

“Cajal and Sherrington’s “neuron doctrine”, which established that the individual neuron is the functional unit of the nervous system [2]”

• cites [2] Shepherd GM 1991 Foundations of the neuron doctrine Oxford Univ PressNot checked yet

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Cnidarian nervous systems are structurally simple.

“The nervous systems of cnidarians, pre-bilaterian animals that diverged close to the base of the metazoan radiation, are structurally simple”

May combine two claims.

Cnidarian and bilaterian nervous systems share many characteristics, whereas ctenophore nervous systems appear fundamentally different, with glutamate and neuropeptides possibly the only neurotransmitters.

“while cnidarian and bilaterian nervous systems have many characteristics in common, those of the Ctenophora appear to differ fundamentally – for example, glutamate and neuropeptides may be the sole neurotransmitters employed [13]”

• cites [13] Moroz LL 2014 The ctenophore genome and the evolutionary origins of neural systems Nature 510 109 14 24847885 PMC4337882 sourceNot checked yet

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Cnidarians are a practical choice for comparative neurobiology; they are a phylum of about 11,000 aquatic animals and the sister clade of Bilateria.

“A more practical choice for such studies are cnidarians, a phylum of approximately 11,000 aquatic animals that occupies a strongly supported position as the sister clade of the Bilateria”

May combine two claims.

Orthologs of synaptic proteins in organisms without nervous systems may have different roles, suggesting that the eumetazoan ancestor co-opted these proteins for neuronal communication.

“whereas orthologs of synaptic proteins may be present in organisms that lack nervous systems, their roles may be quite different [33], suggesting that the eumetazoan ancestor co-opted these to enable neuronal communication”

• cites [33] Burkhardt P 2014 Evolutionary insights into premetazoan functions of the neuronal protein homer Mol Biol Evol 31 2342 2355 24899667 PMC4137706Not checked yet

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The neuropeptide processing enzyme PAM is present in sponges, which lack a nervous system, supporting the idea that amidated peptides originally functioned in communication between epithelial cells.

“the processing machinery for neuropeptides, a dual function peptidylglycine alpha-amidating monooxygenase (PAM), is present in early diverging phyla such as sponges (Porifera) which lack a nervous system, supporting the idea that, within the Metazoa, amidated peptides may have originally functioned in communication between epithelial cells [27]”

• cites [27] Attenborough RMF 2012 A “neural” enzyme in nonbilaterian animals and algae: preneural origins for peptidylglycine α-amidating monooxygenase Mol Biol Evol 29 3095 3109 22496439Not checked yet

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Nervous systems appeared early in animal evolution and were present before the origin of Bilateria.

“nervous systems appeared very early in animal evolution and were certainly in place prior to the origin of bilaterally symmetric animals – also known as Bilateria”

May combine two claims.

Hydra, Nematostella vectensis, Clytia hemispherica, and Hydractinia echinata are laboratory cnidarian species with extensive genomic and transcriptomic resources and available transgenesis and gene-editing technologies.

“the classical freshwater polyp Hydra has been joined in the laboratory by a sea anemone, Nematostella vectensis, a jellyfish, Clytia hemispherica, and a colonial hydrozoan Hydractinia echinata [21]. For each of these species, extensive genomic and transcriptomic resources now exist, and transgenesis and gene-editing technologies are available.”

• cites [21] Technau U Schwaiger M 2015 Recent advances in genomics and transcriptomics of cnidarians Mar Genomics 24 131 138 26421490Not checked yet

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Ctenophora have a controversial phylogenetic position and limited data and technical amenability, making them difficult candidates for comparative neurobiology.

“In addition to the controversial phylogenetic position of the Ctenophora [14,15], a paucity of data and limited amenability to technical approaches make these animals difficult candidates for comparative studies of neurobiology.”

• cites [14] Jékely G 2015 The phylogenetic position of ctenophores and the origin (s) of nervous systems Evodevo 6 1 25905000 PMC4406211 sourceNot checked yet

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• cites [15] Pisani D Liu AG 2015 Animal Evolution: Only Rocks Can Set the Clock Curr Biol 25 R1079 R1081 26583898 sourceNot checked yet

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The patchy distribution of some gene families across Metazoa may result from stochastic gene loss, implying that more extensive taxon sampling may identify more synaptic proteins and require revisiting evolutionary scenarios based on current data.

“The patchy distribution of some gene families across the Metazoa, perhaps resulting from stochastic gene loss [34] implies that more extensive taxon sampling may eventually identify larger numbers of synaptic proteins in both cnidarians and other groups, mandating the revisiting of evolutionary scenarios based on presently available data.”

• cites [34] Forêt S 2010 New tricks with old genes: the genetic bases of novel cnidarian traits Trends Genet 26 154 158 20129693Not checked yet

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Cloning and characterization of transmitter receptors in Cnidaria has been slow and mainly focused on individual gene families, leaving the receptor repertoire mostly unknown.

“In Cnidaria, cloning and characterization of transmitter receptors has in the past been relatively slow and mainly performed by researchers focused on individual gene families [38,39], thus leaving the receptor repertoire of Cnidaria as a mostly unknown territory.”

• cites [38] Golubovic A 2007 A peptide-gated ion channel from the freshwater polyp Hydra J Biol Chem 282 35098 35103 17911098Not checked yet

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• cites [39] Dürrnagel S 2010 Three homologous subunits form a high affinity peptide-gated ion channel in Hydra J Biol Chem 285 11958 11965 20159980 PMC2852933Not checked yet

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Classified as probably not a substantial claim. May combine two claims.

Sponges and placozoans are an outgroup to cnidarians and bilaterians and lack nervous systems, making their data valuable for comparative genomics.

“Since sponges and placozoans represent an “outgroup” to cnidarians and bilaterians (Figure 1), and are phyla of metazoans lacking nervous systems, these data are very valuable for comparative genomic approaches.”

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

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].”

• cites [16] Technau U Steele RE 2011 Evolutionary crossroads in developmental biology: Cnidaria Development 138 1447 1458 21389047 PMC3062418Not checked yet

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• cites [17] Watanabe H 2014 Nodal signalling determines biradial asymmetry in Hydra Nature 515 112 115 25156256Not checked yet

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• cites [18] Kelava I 2015 Evolution of eumetazoan nervous systems: insights from cnidarians Phil Trans R Soc B 370 20150065 26554048 PMC4650132 sourceNot checked yet

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• cites [19] Bosch TCG 2014 Rethinking the role of immunity: lessons from Hydra Trends Immunol 35 495 502 25174994Not checked yet

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• cites [20] Bosch TCG 2014 How do environmental factors influence life cycles and development? An experimental framework for early-diverging metazoans Bio Essays 36 1185 1194 PMC4251966 25205353Not checked yet

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Most structural components of the post-synaptic density are present in the sponge Amphimedon, and some have homologs in choanoflagellates and other unicellular holozoans.

“most of the structural components of the post-synaptic density (PSD) are present in the sponge Amphimedon [22,28], and some have clear homologs in choanoflagellates and other unicellular holozoans [29,30]”

• cites [22] Srivastava M 2010 The Amphimedon queenslandica genome and the evolution of animal complexity Nature 466 720 726 20686567 PMC3130542 sourceNot checked yet

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• cites [28] Sakarya O 2007 A post-synaptic scaffold at the origin of the animal kingdom PLoS One 2 e506 17551586 PMC1876816 sourceNot checked yet

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• cites [29] Suga H 2013 The Capsaspora genome reveals a complex unicellular prehistory of animals Nat Commun 4 PMC3753549 23942320 sourceNot checked yet

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• cites [30] Burkhardt P 2015 The origin and evolution of synaptic proteins– choanoflagellates lead the way J Exp Biol 218 506 514 25696814 sourceNot checked yet

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

Generalizations about early nervous system evolution are currently based on relatively sparse taxon sampling, with whole genome assemblies available for only a few non-bilaterian animals or holozoans.

“A caveat here is that generalizations about early nervous system evolution are currently based on relatively sparse taxon sampling – as yet, whole genome assemblies are available for only a few non-bilaterian animals or holozoans.”

May combine two claims.

The anatomical simplicity of the cnidarian nervous system masks neurophysiological specializations including bidirectional chemical synapses, peptide-gated channels, rapid nematocyst discharge, and axons with two kinds of impulse propagation.

“The anatomical simplicity of the cnidarian nervous system masks some remarkable neurophysiological specializations [35] including, for example, bidirectional chemical synapses (Figure 2) [36,37], signaling by a diversity of peptide-gated channels [38–40], the rapid discharge of nematocysts (Figure 2) [41] and axons with two kinds of impulse propagation [35,42–45].”

• cites [35] Meech RW 2015 Electrogenesis in the lower Metazoa and implications for neuronal integration J Exp Biol 218 537 550 25696817 PMC4334145 sourceNot checked yet

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• cites [36] Horridge GA Mackay B 1962 Naked axons and symmetrical synapses in coelenterates J Cell Sci 3 531 541 14449017Not checked yet

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• cites [37] Anderson PA 1985 Physiology of a bidirectional, excitatory, chemical synapse J Neurophysiol 53 821 835 2984356Not checked yet

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• cites [38] Golubovic A 2007 A peptide-gated ion channel from the freshwater polyp Hydra J Biol Chem 282 35098 35103 17911098Not checked yet

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• cites [39] Dürrnagel S 2010 Three homologous subunits form a high affinity peptide-gated ion channel in Hydra J Biol Chem 285 11958 11965 20159980 PMC2852933Not checked yet

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• cites [40] Assmann M 2014 The comprehensive analysis of DEG/ENaC subunits in Hydra reveals a large variety of peptide-gated channels, potentially involved in neuromuscular transmission BMC Biol 12 1 25312679 PMC4212090Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable).

The difference in neural architecture between cnidarians and bilaterians offers potential for understanding basic design principles and evolutionary trajectories of nervous system circuitry.

“This difference in neural architecture alone offers great potential for understanding the basic design principles and evolutionary trajectories of nervous system circuitry.”

May combine two claims.

CRISPR-Cas9 and related techniques led to a democratization of molecular biology, enabling functional and genomic analyses in many species.

“gene-editing techniques such as CRISPR-Cas9 [11], have led to a “democratization” of molecular biology, with functional and genomic analyses now possible in a wide range of species”

• cites [11] Doudna JA Charpentier E 2014 The new frontier of genome engineering with CRISPR-Cas9 Science (80-) 346 1258096 25430774 sourceNot checked yet

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Some synaptic proteins involved in vesicle exocytosis are represented in unicellular holozoans, and homologs of some SNARE proteins and their interacting partners have been identified in fungi and plants.

“Other classes of “synaptic” proteins, particularly those involved in vesicle exocytosis, are also represented in unicellular holozoans and homologs of some of the SNARE proteins (e.g. synaptobrevin2, syntaxin1) and their interacting partners (e.g. tomosyn) have been even identified in fungi and plants [31].”

• cites [31] Roshchina VV 2016 New trends and perspectives in the evolution of neurotransmitters in microbial, plant, and animal cells Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health 25 77 Springer 26589213Not checked yet

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Phylostratigraphy implies that vertebrate nervous systems originated in the common ancestor of Cnidaria and Bilateria, the Eumetazoa.

“Although phylostratigraphy [26] implies that vertebrate nervous systems have their origins in the common ancestor of Cnidaria and Bilateria (herein referred to as the Eumetazoa)”

• cites [26] Šestak MS 2013 Phylostratigraphic profiles reveal a deep evolutionary history of the vertebrate head sensory systems Front Zool 10 1 23587066 PMC3636138Not checked yet

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Electrophysiological recordings show that cnidarian bidirectional synapses are excitatory, non-polarized, and conduct equally well in either direction.

“Electrophysiological recordings revealed that such bidirectional synapses are excitatory and non-polarized, and conduct equally well in either direction [37].”

• cites [37] Anderson PA 1985 Physiology of a bidirectional, excitatory, chemical synapse J Neurophysiol 53 821 835 2984356Not checked yet

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In Nematostella, specific biogenic amine-synthesizing enzymes are sparse, serotonin is apparently lacking, and aminergic-like transmitters unique to sea anemones act on these receptors.

“Strikingly, specific biogenic amine-synthesizing enzymes are sparse, serotonin is apparently lacking, and it has been concluded that aminergic-like transmitters unique to sea anemones act on these receptors [52].”

• cites [52] Anctil M 2009 Chemical transmission in the sea anemone Nematostella vectensis: A genomic perspective Comp Biochem Physiol Part D Genomics Proteomics 4 268 289 20403752Not checked yet

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Statocysts contain a concretion at their distal part and are surrounded by non-motile mechanosensory cilia.

“Statocysts contain a ‘concretion’ at their distal part, and are surrounded by non-motile mechanosensory cilia [65,66].”

• cites [65] Horridge GA 1969 Statocysts of medusae and evolution of stereocilia Tissue Cell 1 341 353 18631472Not checked yet

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• cites [66] Singla CL 1983 Fine structure of the sensory receptors of Aglantha digitale (Hydromedusae: Trachylina) Cell Tissue Res 231 415 425 6133627Not checked yet

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Genomic analysis of Nematostella reveals several metabotropic glutamate and GABA(B) receptors and a large number of G protein-coupled receptors for monoamines and melatonin.

“the metabotropic and ionotropic receptor repertoire of Nematostella has been inspected by genomic analysis in some detail [52] revealing the presence of several metabotropic glutamate and GABA(B) receptors as well as a large number of G protein-coupled receptors for monoamines and melatonin [52]”

• cites [52] Anctil M 2009 Chemical transmission in the sea anemone Nematostella vectensis: A genomic perspective Comp Biochem Physiol Part D Genomics Proteomics 4 268 289 20403752Not checked yet

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Rhopalia are integrated with the rest of the nervous system, and visual input modulates the pacemaker system that controls contraction of the swimming bell.

“Rhopalia are integrated with the rest of the nervous system [70], and visual input modulates the pacemaker system that controls the contraction of the swimming bell [69,71].”

• cites [70] Garm A 2006 Rhopalia are integrated parts of the central nervous system in box jellyfish Cell Tissue Res 325 333 343 16557386Not checked yet

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• cites [69] Satterlie RA 2014 Multiple conducting systems in the cubomedusa carybdea marsupialis Biol Bull 227 274 284 25572215Not checked yet

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• cites [71] Garm A Bielecki J 2008 Swim pacemakers in box jellyfish are modulated by the visual input J Comp Physiol A 194 641 651 18446348Not checked yet

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Two muscarinic acetylcholine receptors have been identified in Hydra.

“two muscarinic acetylcholine receptors have been identified in Hydra [53]”

• cites [53] Collin C 2013 Two types of muscarinic acetylcholine receptors in Drosophila and other arthropods Cell Mol life Sci 70 3231 3242 23604020 PMC11113683Not checked yet

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The chemical wiring view supports earlier ideas proposed by Carl Pantin.

“We note that this view supports earlier ideas proposed by Carl Pantin [61].”

• cites [61] Pantin CFA 1956 The origin of the nervous system Pubbl Staz Zool Napoli 28 171 181Not checked yet

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Homologous RFamide channels exist in Nematostella and some Protostomia, suggesting that neuropeptides have a broad function in fast neuronal communication.

“Homologous channels also exist in Nematostella [56] and in some Protostomia [59], suggesting that neuropeptides have a broad function in fast neuronal communication.”

• cites [56] Gründer S Assmann M 2015 Peptide-gated ion channels and the simple nervous system of Hydra J Exp Biol 218 551 561 25696818 sourceNot checked yet

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• cites [59] Lingueglia E 1995 Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel Nature 378 730 733 7501021Not checked yet

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Many transmitter-related protein classes in Nematostella are closer to vertebrate than to invertebrate counterparts; octopamine and its receptors are missing.

“many transmitter-related protein classes appeared closer to vertebrate than to invertebrate counterparts; for example, octopamine and its receptors, which are common in invertebrates, are missing in Nematostella [52]”

• cites [52] Anctil M 2009 Chemical transmission in the sea anemone Nematostella vectensis: A genomic perspective Comp Biochem Physiol Part D Genomics Proteomics 4 268 289 20403752Not checked yet

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The diversity of receptor subtypes in cnidarians is in principle comparable to that of chordates and includes AMPA and NMDA receptors, which mediate synaptic plasticity in the vertebrate central nervous system.

“Thus, the diversity of receptor subtypes in cnidarians is, in principle, comparable to that of chordates and notably includes AMPA and NMDA receptors, which mediate synaptic plasticity in the vertebrate central nervous system [54].”

• cites [54] Ryan TJ Grant SGN 2009 The origin and evolution of synapses Nat Rev Neurosci 10 701 712 19738623Not checked yet

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Some cnidarians have elaborate sense organs and perform intricate behaviors that suggest advanced neural integration.

“some cnidarians have elaborate sense organs and perform intricate behaviors (Figure 2) that suggest advanced neural integration”

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Statocysts in Scyphozoa are small tentacle-like organs involved in gravisensation.

“the statocysts in Scyphozoa (Figure 1) are small tentacle-like organs that hang at the outer side of the bell of medusae and are involved in gravisensation”

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

The discharge of nematocysts is one of the fastest processes in biology.

“the discharge of nematocysts is one of the fastest processes in biology”

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The presence of these receptors suggests that the cnidarian nerve net is chemically complex and uses several small molecule transmitters.

“The presence of these receptors suggests that the cnidarian nerve net is chemically complex and uses several small molecule transmitters.”

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

RFamide neuropeptides are present in vertebrates and invertebrates.

“RFamide neuropeptides, which are also present in vertebrates and invertebrates [57]”

• cites [57] Jékely G 2013 Global view of the evolution and diversity of metazoan neuropeptide signaling Proc Natl Acad Sci 110 8702 8707 23637342 PMC3666674Not checked yet

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The presence of these receptors suggests that cnidarians build their nervous systems using essentially the same building blocks as bilaterians, so nervous system evolution may result more from rearrangement of existing molecular components than from invention of novel ones.

“It also suggests that cnidarians build their nervous systems using essentially the same building blocks present in bilaterians, so nervous system evolution may result more from the rearrangement of existing molecular components than the invention of novel ones.”

May combine two claims.

These camera-type eyes enable box jellyfish to avoid obstacles and navigate in water based on terrestrial cues.

“These eyes enable the box jellyfish to avoid obstacles and to navigate in the water based on terrestrial cues [67–69].”

• cites [67] Garm A 2007 Visually guided obstacle avoidance in the box jellyfish Tripedalia cystophora and Chiropsella bronzie J Exp Biol 210 3616 3623 17921163Not checked yet

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• cites [68] Garm A 2011 Box jellyfish use terrestrial visual cues for navigation Curr Biol 21 798 803 21530262Not checked yet

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• cites [69] Satterlie RA 2014 Multiple conducting systems in the cubomedusa carybdea marsupialis Biol Bull 227 274 284 25572215Not checked yet

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The Nematostella genome contains genes for major classes of ionotropic receptors, including nicotinic acetylcholine, AMPA, kainate, NMDA, GABA(A), and P2X receptors; only a 5-HT3 receptor homolog is apparently lacking.

“the Nematostella genome contains several genes for the major classes of ionotropic receptors (nicotinic acetylcholine receptors, glutamate receptors of the AMPA, kainate and NMDA type, GABA(A), and P2X); only an 5-HT3 receptor homolog is apparently lacking [52]”

• cites [52] Anctil M 2009 Chemical transmission in the sea anemone Nematostella vectensis: A genomic perspective Comp Biochem Physiol Part D Genomics Proteomics 4 268 289 20403752Not checked yet

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The diversity of ion channel receptors in Cnidaria contrasts with the relative paucity of ion channel families in ctenophores, supporting views of independent neural evolution in Ctenophora.

“the diversity of ion channel receptors in Cnidaria is in stark contrast to the relative paucity of ion channel families present in ctenophores, supporting views of independent neural evolution in the Ctenophora [13]”

• cites [13] Moroz LL 2014 The ctenophore genome and the evolutionary origins of neural systems Nature 510 109 14 24847885 PMC4337882 sourceNot checked yet

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Nematocyst discharge is triggered by mechanical stimulation and employs the fast-recoiling protein cnidoin, which stores kinetic energy in the nematocyst capsule.

“This discharge is triggered by mechanical stimulation, and employs a fast-recoiling silk-like elastic protein, cnidoin, that incorporates into the capsule of the nematocyst and stores kinetic energy [41].”

• cites [41] Beckmann A 2015 A fast recoiling silk-like elastomer facilitates nanosecond nematocyst discharge BMC Biol 13 1 25592740 PMC4321713Not checked yet

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Classified as probably not a substantial claim.

The apparent complexity of the cnidarian nerve net makes it possible that cnidarians use a chemical connectome, a sophisticated agonist-receptor matching space that implements selectivity for specific behavioral patterns.

“This apparent complexity makes it possible that cnidarians use a “chemical connectome” [60], i.e., a sophisticated chemical agonist-receptor matching space that implements the selectivity necessary for specific behavioral patterns.”

• cites [60] Andrews AM 2013 The BRAIN Initiative: Toward a Chemical Connectome ACS Chem Neurosci 4 645 23862750 PMC3656756Not checked yet

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Nematocysts and the ciliary-microvillar sensory apparatus of some cnidarian mechanosensory cells are structurally similar, suggesting they are evolutionarily related.

“There is a striking structural similarity between nematocysts and the ciliary-microvillar sensory apparatus of mechanosensory cells in some cnidarians [62,63], suggesting that nematocysts and mechanosensory structures are evolutionarily related.”

• cites [62] Mattern CFT 1965 Electron microscope observations on the structure and discharge of the stenotele of Hydra J Cell Biol 27 621 638 4380091 PMC2106766Not checked yet

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• cites [63] Tardent P Schmid V 1972 Ultrastructure of mechanoreceptors of the polyp Coryne pintneri (Hydrozoa, Athecata) Exp Cell Res 72 265 275 4402012Not checked yet

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Ciliated mechanosensory cells in cnidarians are similar to vertebrate hair cells and may represent descendants of an ancient metazoan sensory cell type.

“The ciliated mechanosensory cells in cnidarians are also similar to the hair cells of vertebrates, and may represent descendants of an ancient metazoan sensory cell type [64].”

• cites [64] Arendt D 2015 Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution Phil Trans R Soc B 370 20150286 26554050 PMC4650134 sourceNot checked yet

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The giant axon system of Aglantha digitale is an advanced specialization that has been extensively studied because it is amenable to electrophysiological recordings.

“The giant axon system of a hydrozoan Aglantha digitale (Figure 1) represents an advanced specialization that has been extensively studied due to its amenability to electrophysiological recordings [42,45,73–78].”

• cites [42] Mackie G Meech R 1995 Central circuitry in the jellyfish Aglantha. I: The relay system J Exp Biol 198 2261 2270 9320176Not checked yet

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• cites [45] Mackie G Meech R 1995 Central circuitry in the jellyfish Aglantha. II: The ring giant and carrier systems J Exp Biol 198 2271 2278 9320190Not checked yet

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• cites [73] Mackie GO Meech RW 2000 Central circuitry in the jellyfish Aglantha digitale. III The rootlet and pacemaker systems J Exp Biol 203 1797 1807 10821737Not checked yet

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• cites [74] Mackie GO 2003 Central circuitry in the jellyfish Aglantha digitale IV. Pathways coordinating feeding behaviour J Exp Biol 206 2487 2505 12796463Not checked yet

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• cites [75] Mackie GO 1992 Giant axons and escape swimming in Euplokamis dunlapae (Ctenophora: Cydippida) Biol Bull 182 248 256 29303667 sourceNot checked yet

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• cites [76] Mackie GO 2004 Central neural circuitry in the jellyfish Aglantha Neurosignals 13 5 19 15004422Not checked yet

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• cites [77] Roberts A Mackie GO 1980 The giant axon escape system of a hydrozoan medusa, Aglantha digitale J Exp Biol 84 303 318 6102591Not checked yet

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• cites [78] Kerfoot PA 1985 Neuromuscular transmission in the jellyfish Aglantha digitale J Exp Biol 116 1 25 2865323Not checked yet

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Cnidarians can rebuild any missing body part, including generating large numbers of new nerve cells that connect with the existing nervous system.

“The spectacular ability to rebuild any missing body part includes the generation of large numbers of new nerve cells that seamlessly connect with the remains of the existing nervous system”

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

Courting behavior, called the wedding dance, has been described for some cubozoan medusae.

“Another impressive behaviour among cnidarians is the ‘wedding dance’, or courting behaviour described for some cubozoan medusae [90].”

• cites [90] Werner B 1973 Spermatozeugmen und paarungsverhalten bei Tripedalia cystophora (Cubomedusae) Mar Biol 18 212 217Not checked yet

  Not checked in the free run.

May combine two claims.

During mating in Carybdea sivickisi, the male attaches a tentacle to the female, brings their manubriums into contact, forms a spermatophore, transfers it to a female tentacle, and the female inserts it into her manubrium.

“During mating, the male attaches a tentacle to the female and brings their oral openings (manubriums) into direct contact. The male forms a spermatophore, which is then transferred to one of the female’s tentacles. Following release by the male, the female inserts the spermatophore into her manubrium [91].”

• cites [91] Lewis C Long TAF 2005 Courtship and reproduction in Carybdea sivickisi (Cnidaria: Cubozoa) Mar Biol 147 477 483Not checked yet

  Not checked in the free run.

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

Spontaneous rhythmic pulsation of tentacles in soft corals was first noted by Lamarck nearly 200 years ago.

“spontaneous rhythmic pulsation of tentacles in soft corals (as Xenia, Anthozoa, Figure 1) [84] were first noted by Lamarck nearly 200 years ago”

• cites [84] Kremien M 2013 Benefit of pulsation in soft corals Proc Natl Acad Sci 110 8978 8983 23610420 PMC3670383Not checked yet

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

Cnidarians have a long history as experimental animals for whole body regeneration, beginning with Trembley's bisection experiments and Brown's transplant experiments.

“Cnidarians have a long history as experimental animals for whole body regeneration beginning with Abraham Trembley’s bisection experiments in 1744 [81] and the classic “developmental organizer” transplant experiments of Ethel Brown in Thomas Morgan’s lab [94].”

• cites [81] Trembley A 1744 Mémoires pour servir à l’histoire d’un genre de polypes d’eau douce, à bras en forme de cornes. Par A. Trembley Jean chez Verbeek HermanNot checked yet

  Not checked in the free run.

• cites [94] Browne EN 1909 The production of new hydranths in hydra by the insertion of small grafts J Exp Zool 7 1 23Not checked yet

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

Feeding behavior of Hydra polyps can be monitored with a dissection microscope and video-recorded to register and quantify the sequence and timing of events.

“Feeding behavior of the polyps can be easily monitored using a dissection microscope, and video-recorded to register and quantify sequence and timing of the events.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

As a single footed polyp, Hydra cannot translate its position in the bottom of fresh water ponds and rivers without being carried away by the current.

“As a single footed polyp, Hydra cannot translate its position in the bottom of fresh water ponds and rivers without being carried away by the current.”

May combine two claims.

During slow swimming, low-amplitude Ca2+ spikes drive weak muscle contractions, whereas during predator avoidance the jellyfish switches to fast escape swimming that relies on strong contractions elicited by rapidly conducted Na+-dependent action potentials.

“During slow swimming, low amplitude Ca2+ spikes drive weak muscle contractions, but during predator avoidance the jellyfish switches to fast escape swimming that relies on strong contractions elicited by rapidly conducted Na+-dependent action.”

• cites [79] Mackie GO Meech RW 1985 Separate sodium and calcium spikes in the same axon 2858055Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable).

Understanding how the cnidarian neurogenic program is activated throughout both germ layers and during regeneration has the potential to stimulate research to improve the generation of neurons in human patients.

“understanding in detail how the cnidarian neurogenic program can be promiscuously activated throughout both germ layers of the embryo and during regeneration has the potential to stimulate research to improve the generation of neurons in pathological conditions in human patients.”

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

In Cassiopea medusae, spontaneous rhythmic pulsations of the bell have been investigated for the influence of sense organs and overall nervous system control.

“Among medusae, such as Cassiopea (Scyphozoa, Figure 1) the spontaneous rhythmic pulsations of the medusa bell present a behavior pattern in which the influence of certain sense organs and the overall control of the nervous system has been investigated [85,86].”

• cites [85] Hamlet C 2011 A numerical study of the effects of bell pulsation dynamics and oral arms on the exchange currents generated by the upside-down jellyfish Cassiopea xamachana J Exp Biol 214 1911 1921 21562179Not checked yet

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• cites [86] Santhanakrishnan A 2012 Flow structure and transport characteristics of feeding and exchange currents generated by upside-down Cassiopea jellyfish J Exp Biol 215 2369 2381 22723475Not checked yet

  Not checked in the free run.

May combine two claims.

The molecular control of neurogenesis in cnidarians is remarkably similar to that in vertebrates: Notch signaling controls the number of neural progenitor cells, soxB and bHLH transcription factor genes regulate their development, and Wnt signaling gradients pattern the nervous system.

“The molecular control of neurogenesis is remarkably similar to that in vertebrates: Notch signalling controls the number of neural progenitor cells, soxB and bHLH transcription factor encoding genes regulate their further development and Wnt signaling gradients are involved in the patterning of the nervous system [99–101].”

• cites [99] Layden MJ 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 22318631 PMC3274362Not checked yet

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• cites [100] Richards GS Rentzsch F 2014 Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis Development 141 4681 4689 25395455 sourceNot checked yet

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• cites [101] Watanabe H 2014 Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis Nat Commun 5 PMC4284808 25534229 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The use of cell type-specific promoters for reporter genes has improved the visualization of neuronal morphology and the tracking of the developmental origin of nerve cells.

“The use of cell type-specific promoters for reporter genes has also improved the visualization of neuronal morphology and tracking of the developmental origin of nerve cells [98,100].”

• cites [98] Nakanishi N 2012 Nervous systems of the sea anemone Nematostella vectensis are generated by ectoderm and endoderm and shaped by distinct mechanisms Development 139 347 357 22159579Not checked yet

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• cites [100] Richards GS Rentzsch F 2014 Transgenic analysis of a SoxB gene reveals neural progenitor cells in the cnidarian Nematostella vectensis Development 141 4681 4689 25395455 sourceNot checked yet

  Not checked in the free run.

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

Abraham Trembley first described somersaulting locomotion in Hydra in the 18th century.

“Abraham Trembley first described somersaulting locomotion in Hydra [81]”

• cites [81] Trembley A 1744 Mémoires pour servir à l’histoire d’un genre de polypes d’eau douce, à bras en forme de cornes. Par A. Trembley Jean chez Verbeek HermanNot checked yet

  Not checked in the free run.

May combine two claims.

This mating behavior includes recognition of the other sex and assessment of sexual maturity.

“This behaviour includes elements of recognition of the other sex and the assessment of sexual maturity.”

May combine two claims.

Hydra somersaulting involves bending its body wall, attaching its tentacles and mouth to the substrate, releasing its foot, swinging its body over to reattach its foot ahead of the mouth, and then releasing the mouth to become erect again.

“Hydra bends its body wall, attaches its tentacles and mouth to the substrate, releases its foot, swings its body over to reattach its foot ahead of the mouth, and then releases the mouth to become erect again.”

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

It is currently not understood how Hydra somersaulting is achieved via a diffuse net of neurons.

“It is currently not at all understood how this complicated behavior, which indeed not all humans can master, is achieved via a diffuse net of neurons.”

Classified as probably not a substantial claim.

The spatially broad neurogenic potential of cnidarians poses specific challenges for the developmental control of neurogenesis, such as regulating the balance between neural and non-neural cell types and determining the number of neural progenitor cells.

“The spatially broad neurogenic potential of cnidarians poses specific challenges for the developmental control of neurogenesis, e.g. how is the balance between neural and non-neural cell types regulated? Which mechanisms determine the number of neural progenitor cells?”

May combine two claims.

This complexity and functional sophistication contrasts with the default concept of a simple nerve net in cnidarians and indicates that Aglantha has found ways to implement different behaviors using the same available hardware.

“This complexity and functional sophistication stands in contrast to the default concept of a simple nerve net in cnidarians, and indicates that Aglantha has found ingenious ways to implement different behaviors using the same available “hardware”.”

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

Growth pulsations are thought to be essential for growth and morphogenesis of colonial hydroid polyps.

“growth pulsations, i.e. successive rhythmic extensions and retractions of the shoot and stolon growing tips, are thought to be essential for growth and morphogenesis of colonial hydroid polyps (Hydrozoa, Figure 1) [87–89]”

• cites [87] Labas YA 1981 On Pulsating Growth in Multicellular Organisms Dokl Akad Nauk SSSR 257 1247 1250Not checked yet

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• cites [88] Beloussov LV 1993 Growth pulsations in hydroid polyps: kinematics, biological role and cytophysiology Oscil MorphogNot checked yet

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• cites [89] Kosevich IA 2006 Mechanics of growth pulsations as the basis of growth and morphogenesis in colonial hydroids Russ J Dev Biol 37 90 101 16634200Not checked yet

  Not checked in the free run.

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

In the sexually dimorphic cubomedusa Carybdea sivickisi, sexually mature females produce conspicuous velar spots and males court only females with these spots.

“In the sexually dimorphic cubomedusa Carybdea sivickisi (Cubozoa, Figure 1), sexually mature females produce conspicuous velar spots and males only court females with these spots.”

May combine two claims.

Stable transgenesis was first achieved in Hydra and is now also available in Nematostella and Hydractinia.

“Stable transgenesis was first achieved in Hydra [102] and is also now available in both Nematostella and Hydractinia [103,104] (Figure 2).”

• cites [102] Wittlieb J 2006 Transgenic Hydra allow in vivo tracking of individual stem cells during morphogenesis Proc Natl Acad Sci U S A 103 6208 11 16556723 PMC1458856Not checked yet

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• cites [103] Renfer E 2010 A muscle-specific transgenic reporter line of the sea anemone, Nematostella vectensis Proc Natl Acad Sci 107 104 108 20018670 PMC2806778Not checked yet

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• cites [104] Künzel T 2010 Migration and differentiation potential of stem cells in the cnidarian Hydractinia analysed in eGFP-transgenic animals and chimeras Dev Biol 348 120 129 20800060Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Dynamical attractors are very difficult to identify and manipulate in most laboratory species because functional recordings of activity are always incomplete.

“These attractors are very difficult to identify and manipulate in most laboratory species, due to the fact that functional recordings of the activity are always incomplete.”

May combine two claims.

Non-canonical functions of nervous systems may include roles in regeneration, development of innervated tissues, tissue homeostasis, and bidirectional communication with the commensal microbiota.

“Non-canonical functions may include a role in regeneration, development of innervated tissues, and tissue homeostasis [113,114] as well as bidirectional communication with the commensal microbiota [115–120].”

• cites [113] Ivashkin E 2014 A paradigm shift in neurobiology: peripheral nerves deliver cellular material and control development Zoology 117 293 294 25175371 sourceNot checked yet

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• cites [114] Adameyko I Fried K 2016 The nervous system orchestrates and integrates craniofacial development: a review Front Physiol 7 PMC4759458 26924989 sourceNot checked yet

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• cites [115] Yano JM 2015 Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis Cell 161 264 276 25860609 PMC4393509 sourceNot checked yet

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• cites [116] Williams BB 2014 Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine Cell Host Microbe 16 495 503 25263219 PMC4260654 sourceNot checked yet

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• cites [117] Barrett E 2012 γ-Aminobutyric acid production by culturable bacteria from the human intestine J Appl Microbiol 113 411 417 22612585 sourceNot checked yet

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• cites [118] Cryan JF Dinan TG 2012 Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour Nat Rev Neurosci 13 701 712 22968153 sourceNot checked yet

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• cites [119] Forsythe P Kunze WA 2013 Voices from within: gut microbes and the CNS Cell Mol life Sci 70 55 69 22638926 PMC11113561 sourceNot checked yet

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• cites [120] Mu C 2016 Gut microbiota: the brain peacekeeper Front Microbiol 7 PMC4794499 27014255 sourceNot checked yet

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Classified as probably not a substantial claim.

The original function of the nervous system remains somewhat mysterious.

“Distressingly, the original function of the nervous system remains somewhat mysterious [112].”

• cites [112] Jekely G 2015 An option space for early neural evolution Phil Trans R Soc B 370 20150181 26554049 PMC4650133Not checked yet

  Not checked in the free run.

May combine two claims.

Caenorhabditis and Drosophila are highly diverged organisms with high levels of gene loss and sequence divergence, whereas at least some cnidarians have retained much of the ancestral genetic complexity of metazoans.

“diverged organisms characterized by high levels of gene loss and sequence divergence, whereas at least some cnidarians have retained much of the ancestral genetic complexity of metazoans [108–110].”

• cites [108] Kortschak RD 2003 EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates Curr Biol 13 2190 2195 14680636Not checked yet

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• cites [109] Technau U 2005 Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians TRENDS Genet 21 633 639 16226338 sourceNot checked yet

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• cites [110] Raible F Arendt D 2004 Metazoan evolution: some animals are more equal than others Curr Biol 14 R106 R108 14986636Not checked yet

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