Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation
Open accessAbstract
BACKGROUND: Cellular differentiation is a critical process during development of multicellular animals that must be tightly controlled in order to avoid precocious differentiation or failed generation of differentiated cell types. Research in flies, vertebrates, and nematodes has led to the identification of a conserved role for Notch signaling as a mechanism to regulate cellular differentiation regardless of tissue/cell type. Notch signaling can occur through a canonical pathway that results in the activation of hes gene expression by a complex consisting of the Notch intracellular domain, SuH, and the Mastermind co-activator. Alternatively, Notch signaling can occur via a non-canonical mechanism that does not require SuH or activation of hes gene expression. Regardless of which mechanism is being used, high Notch activity generally inhibits further differentiation, while low Notch activity promotes differentiation. Flies, vertebrates, and nematodes are all bilaterians, and it is therefore unclear if Notch regulation of differentiation is a bilaterian innovation, or if it represents a more ancient mechanism in animals. RESULTS: To reconstruct the ancestral function of Notch signaling we investigate Notch function in a non-bilaterian animal, the sea anemone Nematostella vectensis (Cnidaria). Morpholino or pharmacological knockdown of Nvnotch causes increased expression of the neural differentiation gene NvashA. Conversely, overactivation of Notch activity resulting from overexpression of the Nvnotch intracellular domain or by overexpression of the Notch ligand Nvdelta suppresses NvashA. We also knocked down or overactivated components of the canonical Notch signaling pathway. We disrupted NvsuH with morpholino or by overexpressing a dominant negative NvsuH construct. We saw no change in expression levels for Nvhes genes or NvashA. Overexpression of Nvhes genes did not alter NvashA expression levels. Lastly, we tested additional markers associated with neuronal differentiation and observed that non-canonical Notch signaling broadly suppresses neural differentiation in Nematostella. CONCLUSIONS: We conclude that one ancestral role for Notch in metazoans was to regulate neural differentiation. Remarkably, we found no evidence for a functional canonical Notch pathway during Nematostella embryogenesis, suggesting that the non-canonical hes-independent Notch signaling mechanism may represent an ancestral Notch signaling pathway.
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Notch/Delta function in neurogenesis in Nematostella is not conducted through the canonical pathway involving Su(H), but through a non-canonical, yet unidentified route.
“More surprising was the finding that the Notch/Delta function in neurogenesis is not conducted through the canonical pathway, i.e. involving suppressor of hairy (Su(H)), but a non-canonical, yet unidentified route [61].”
From Evolution of eumetazoan nervous systems: insights from cnidarians (2015) · cites this paper as [61]
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].”
From Evolution of eumetazoan nervous systems: insights from cnidarians (2015) · cites this paper as [61]
In that ancestor, epithelial cells were singled out to become neurons by a cell-determining system such as the Notch/Delta system.
“which were singled out to become neurons by a cell-determining system (e.g. the Notch/Delta system) [61]”
From Evolution of eumetazoan nervous systems: insights from cnidarians (2015) · cites this paper as [61]
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Cites
Notch signalling: a simple pathway becomes complex
Bray, S. J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2009 · Cited by 2,620 · see citing works
Broad phylogenomic sampling improves resolution of the animal tree of life
Dunn, C. W., Hejnol, A., Matus, D. Q., Pang, K., Browne, W. E., Smith, S. A., Seaver, E., Rouse, G. W., Obst, M., Edgecombe, G. D., et al. (2008) · Nature · doi:10.1038/nature06614 · Cited by 1,921 · cited 1× · see citing works
“They are the ctenophores, poriferans, placozoans, and cnidarians, with cnidarians being the most closely related to bilaterians [1-4].”
Self-citationProneural genes and the specification of neural cell types
Bertrand, N., Castro, D. S., & Guillemot, F. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn874 · Cited by 1,572 · see citing works
Sea Anemone Genome Reveals Ancestral Eumetazoan Gene Repertoire and Genomic Organization
Putnam, N. H., Srivastava, M., Hellsten, U., Dirks, B., Chapman, J., Salamov, A., Terry, A., Shapiro, H., Lindquist, E., Kapitonov, V. V., et al. (2007) · Science · doi:10.1126/science.1139158 · Cited by 1,555 · see citing works
Self-citationThe Amphimedon queenslandica genome and the evolution of animal complexity
Srivastava, M., Simakov, O., Chapman, J., Fahey, B., Gauthier, M. E. A., Mitros, T., Richards, G. S., Conaco, C., Dacre, M., Hellsten, U., et al. (2010) · Nature · doi:10.1038/nature09201 · Cited by 1,049 · see citing works
The Trichoplax genome and the nature of placozoans
Srivastava, M., Begovic, E., Chapman, J., Putnam, N. H., Hellsten, U., Kawashima, T., Kuo, A., Mitros, T., Salamov, A., Carpenter, M. L., et al. (2008) · Nature · doi:10.1038/nature07191 · Cited by 889 · see citing works
Functional gamma‐secretase inhibitors reduce beta‐amyloid peptide levels in brain
Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., Andrieu, P. D. S. I., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E. G., Holsztynska, E. J., et al. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00012.x · Cited by 870 · see citing works
Chapman, J. A., Kirkness, E. F., Simakov, O., Hampson, S. E., Mitros, T., Weinmaier, T., Rattei, T., Balasubramanian, P. G., Borman, J., Busam, D., et al. (2010) · Nature · doi:10.1038/nature08830 · Cited by 810 · see citing works
Oscillations in Notch Signaling Regulate Maintenance of Neural Progenitors
Shimojo, H., Ohtsuka, T., & Kageyama, R. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.014 · Cited by 706 · see citing works
The Genome of the Ctenophore <i>Mnemiopsis leidyi</i> and Its Implications for Cell Type Evolution
Ryan, J. F., Pang, K., Schnitzler, C. E., Nguyen, A.-D., Moreland, R. T., Simmons, D. K., Koch, B. J., Francis, W. R., Havlak, P., Program, N. C. S., et al. (2013) · Science · doi:10.1126/science.1242592 · Cited by 702 · see citing works
Self-citationThe Hes gene family: repressors and oscillators that orchestrate embryogenesis
Kageyama, R., Ohtsuka, T., & Kobayashi, T. (2007) · Development · doi:10.1242/dev.000786 · Cited by 683 · see citing works
Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants
Ye, Y., Lukinova, N. I., & Fortini, M. (1999) · Nature · doi:10.1038/19096 · Cited by 492 · see citing works
Kopan, R., Nye, J. S., & Weintraub, H. (1994) · Development · doi:10.1242/dev.120.9.2385 · Cited by 488 · see citing works
Cubas, P., de Celis, J. F., Campuzano, S., & Modolell, J. (1991) · Genes & Development · doi:10.1101/gad.5.6.996 · Cited by 452 · see citing works
Lecourtois, M., & Schweisguth, F. (1995) · Genes & Development · doi:10.1101/gad.9.21.2598 · Cited by 430 · see citing works
Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway
Shawber, C. J., Nofziger, D., Hsieh, J. J.-D., Lindsell, C. E., Bögler, O., Hayward, D. W., & Weinmaster, G. (1996) · Development · doi:10.1242/dev.122.12.3765 · Cited by 367 · see citing works
Canonical and Non-Canonical Notch Ligands
D’Souza, B., Meloty-Kapella, L., & Weinmaster, G. (2010) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)92003-6 · Cited by 364 · see citing works
Notch Signaling in the Regulation of Stem Cell Self-Renewal and Differentiation
Liu, J., Sato, C., Cerletti, M., & Wagers, A. J. (2010) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)92012-7 · Cited by 309 · see citing works
Stem cells living with a Notch
Koch, U., Lehal, R., & Radtke, F. (2013) · Development · doi:10.1242/dev.080614 · Cited by 283 · see citing works
Origin and evolution of the Notch signalling pathway: an overview from eukaryotic genomes
Gazave, E., Lapébie, P., Richards, G. S., Brunet, F., Ereskovsky, A. V., Degnan, B. M., Borchiellini, C., Vervoort, M., & Renard, E. (2009) · BMC Evolutionary Biology · doi:10.1186/1471-2148-9-249 · Cited by 266 · see citing works
Marlow, H. Q., Srivastava, M., Matus, D. Q., Rokhsar, D., & Martindale, M. Q. (2009) · Developmental Neurobiology · doi:10.1002/dneu.20698 · Cited by 247 · see citing works
Self-citationChoosing a cell fate: a view from the Notch locus
Artavanis‐Tsakonas, S., & Simpson, P. (1991) · Trends in Genetics · doi:10.1016/0168-9525(91)90264-q · Cited by 210 · see citing works
Choosing a cell fate: a view from the Notch locus
Artavanis‐Tsakonas, S. (1991) · Trends in Genetics · doi:10.1016/0168-9525(91)90220-k · Cited by 199 · see citing works
Nakanishi, N., Renfer, E., Technau, U., & Rentzsch, F. (2012) · Development · doi:10.1242/dev.071902 · Cited by 188 · see citing works
The Bilaterian Head Patterning Gene six3/6 Controls Aboral Domain Development in a Cnidarian
Sinigaglia, C., Busengdal, H., Leclère, L., Technau, U., & Rentzsch, F. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001488 · Cited by 169 · see citing works
Origins of neurogenesis, a cnidarian view
Galliot, B., Quiquand, M., Ghila, L., de Rosa, R., Miljkovic-Licina, M., & Chera, S. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.05.563 · Cited by 168 · see citing works
Genomic inventory and expression of Sox and Fox genes in the cnidarian Nematostella vectensis
Magie, C. R., Pang, K., & Martindale, M. Q. (2005) · Development Genes and Evolution · doi:10.1007/s00427-005-0022-y · Cited by 158 · see citing works
Self-citationFunctional roles of Notch signaling in the cnidarian Nematostella vectensis
Marlow, H. Q., Röttinger, É., Boekhout, M., & Martindale, M. Q. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.11.012 · Cited by 101 · see citing works
Self-citationThe Notch signaling pathway in the cnidarian Hydra
Käsbauer, T., Towb, P., Alexandrova, O., David, C. N., Dall'Armi, E., Staudigl, A., Stiening, B., & Böttger, A. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.11.022 · Cited by 99 · see citing works
Layden, M. J., Boekhout, M., & Martindale, M. Q. (2012) · Development · doi:10.1242/dev.073221 · Cited by 98 · see citing works
Self-citationNon-canonical activation of Notch signaling/target genes in vertebrates
Sanalkumar, R., Bindu, D. S., & James, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0391-x · Cited by 91 · see citing works
Morphological and Molecular Analysis of the Nematostella vectensis Cnidom
Zenkert, C., Takahashi, T., Diesner, M.-O., & Özbek, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022725 · Cited by 90 · see citing works
Molecular separation of two signaling pathways for the receptor, Notch
Gall, M. L., Mattei, C. D., & Giniger, E. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.10.030 · Cited by 86 · see citing works
Stasiuk, S. J., Scott, M. J., & Grant, W. N. (2012) · EvoDevo · doi:10.1186/2041-9139-3-1 · Cited by 84 · see citing works
Layden, M. J., Röttinger, É., Wolenski, F. S., Gilmore, T. D., & Martindale, M. Q. (2013) · Nature Protocols · doi:10.1038/nprot.2013.009 · Cited by 81 · see citing works
Self-citationBiodiversity and Noncanonical Notch Signaling
Heitzler, P. (2010) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(10)92014-0 · Cited by 72 · see citing works
Wolenski, F. S., Layden, M. J., Martindale, M. Q., Gilmore, T. D., & Finnerty, J. R. (2013) · Nature Protocols · doi:10.1038/nprot.2013.014 · Cited by 69 · see citing works
Self-citationNotch and the choice of cell fate in Drosophila neuroepithelium
Simpson, P. (1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90260-d · Cited by 67 · see citing works
Notch-signalling is required for head regeneration and tentacle patterning in Hydra
Münder, S., Tischer, S., Grundhuber, M., Büchels, N., Bruckmeier, N., Eckert, S., Seefeldt, C. A., Prexl, A., Käsbauer, T., & Böttger, A. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.08.022 · Cited by 51 · see citing works
Richards, G. S., & Degnan, B. M. (2012) · EvoDevo · doi:10.1186/2041-9139-3-15 · Cited by 50 · see citing works
Layden, M. J., Meyer, N. P., Pang, K., Seaver, E. C., & Martindale, M. Q. (2010) · EvoDevo · doi:10.1186/2041-9139-1-12 · Cited by 46 · see citing works
Self-citationGenikhovich, G., & Technau, U. (2011) · Development · doi:10.1242/dev.068122 · Cited by 35 · see citing works
The vascular origin of hematopoietic cells
Adamo, L., & García‐Cardeña, G. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.09.008 · Cited by 32 · see citing works
Studies on the nematosomes ofNematostella vectensisStephenson (Coelenterata: Actiniaria)
Williams, R. B. (1979) · Journal of Natural History · doi:10.1080/00222937900770061 · Cited by 16 · see citing works
The hybridoma revolution: an offshoot of basic research
Milstein, C. (1999) · BioEssays · doi:10.1002/(sici)1521-1878(199911)21:11 · Cited by 9 · see citing works
V.—Diagnoses of new species and a new genus of Pycnogonida in the South African, Museum
Barnard, K. H. (1946) · Annals and Magazine of Natural History · doi:10.1080/00222934608654521 · Cited by 6 · see citing works
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Notch Signaling in Development, Tissue Homeostasis, and Disease
Siebel, C., & Lendahl, U. (2017) · Physiological Reviews · doi:10.1152/physrev.00005.2017 · Cited by 968 · see citing works
Layden, M. J., Rentzsch, F., & Röttinger, É. (2016) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.222 · Cited by 148 · see citing works
Self-citationThe cellular and molecular basis of cnidarian neurogenesis
Rentzsch, F., Layden, M. J., & Manuel, M. (2016) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.257 · Cited by 95 · see citing works
Self-citationStepwise emergence of the neuronal gene expression program in early animal evolution
Najle, S. R., Grau‐Bové, X., Elek, A., Navarrete, C., Cianferoni, D., Chiva, C., Cañas-Armenteros, D., Mallabiabarrena, A., Kamm, K., Sabidó, E., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.027 · Cited by 86 · see citing works
Phylogenetic evidence for the modular evolution of metazoan signalling pathways
Babonis, L. S., & Martindale, M. Q. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2015.0477 · Cited by 86 · see citing works
Self-citationEvolution of eumetazoan nervous systems: insights from cnidarians
Kelava, I., Rentzsch, F., & Technau, U. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0065 · Cited by 84 · see citing works
Regulation of Nematostella neural progenitors by SoxB, Notch and bHLH genes
Richards, G. S., & Rentzsch, F. (2015) · Development · doi:10.1242/dev.123745 · Cited by 80 · see citing works
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Li, X., Zhai, W., & Teng, C.-B. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms17010048 · Cited by 64 · see citing works
Tournière, O., Dolan, D., Richards, G. S., Sunagar, K., Columbus-Shenkar, Y. Y., Moran, Y., & Rentzsch, F. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.031 · Cited by 74 · see citing works
Warner, J. F., Guerlais, V., Amiel, A., Johnston, H. T., Nedoncelle, K., & Röttinger, É. (2018) · Development · doi:10.1242/dev.162867 · Cited by 70 · see citing works
Manzari‐Tavakoli, A., Babajani, A., Farjoo, M. H., Hajinasrollah, M., Bahrami, S., & Niknejad, H. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.827275 · Cited by 62 · see citing works
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Layden, M. J., Johnston, H. T., Amiel, A., Havrilak, J. A., Steinworth, B. M., Chock, T., Röttinger, É., & Martindale, M. Q. (2016) · BMC Biology · doi:10.1186/s12915-016-0282-1 · Cited by 62 · see citing works
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Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis
Zeng, C., Xing, R., Liu, J., & Xing, F. (2015) · APOPTOSIS · doi:10.1007/s10495-015-1188-z · Cited by 54 · see citing works
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Favarolo, M. B., & López, S. L. (2018) · Mechanisms of Development · doi:10.1016/j.mod.2018.06.005 · Cited by 44 · see citing works
Kidd, S., Struhl, G., & Lieber, T. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005244 · Cited by 42 · see citing works
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Gazave, E., B., L. Q. I., & Balavoine, G. (2017) · Open Biology · doi:10.1098/rsob.160242 · Cited by 42 · see citing works
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Havrilak, J. A., Faltine-Gonzalez, D. Z., Wen, Y., Fodera, D. M., Simpson, A. C., Magie, C. R., & Layden, M. J. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.08.028 · Cited by 37 · see citing works
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Busengdal, H., & Rentzsch, F. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.08.021 · Cited by 35 · see citing works
Recent advances in genomics and transcriptomics of cnidarians
Technau, U., & Schwaiger, M. (2015) · Marine Genomics · doi:10.1016/j.margen.2015.09.007 · Cited by 35 · see citing works
Genomics and development of Nematostella vectensis and other anthozoans
Rentzsch, F., & Technau, U. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.05.024 · Cited by 32 · see citing works
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Schwaiger, M., Andrikou, C., Dnyansagar, R., Murguia, P. F., Paganos, P., Voronov, D., Zimmermann, B., Lebedeva, T. S., Schmidt, H. A., Genikhovich, G., et al. (2022) · Nature Ecology & Evolution · doi:10.1038/s41559-022-01905-w · Cited by 29 · see citing works
Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective
Lv, Y., Pang, X., Cao, Z., Song, C., Liu, B., Wu, W., & Pang, Q. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063322 · Cited by 25 · see citing works
Tournière, O., Gahan, J. M., Busengdal, H., Bartsch, N., & Rentzsch, F. (2022) · Science Advances · doi:10.1126/sciadv.abi7109 · Cited by 25 · see citing works
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Baker, E. C., Layden, M. J., van Rossum, D. B., Kamel, B., Medina, M., Simpson, E., & Jegla, T. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142730 · Cited by 23 · see citing works
Self-citationGahan, J. M., Kouzel, I. U., Jansen, K. O., Burkhardt, P., & Rentzsch, F. (2022) · Nature Communications · doi:10.1038/s41467-022-28107-z · Cited by 19 · see citing works
Technau, U., Genikhovich, G., & Kraus, J. E. M. (2015) · Springer eBooks · doi:10.1007/978-3-7091-1862-7_6 · Cited by 17 · see citing works
Segregation of endoderm and mesoderm germ layer identities in the diploblast Nematostella vectensis
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Sinkovics, J. (2015) · International Journal of Oncology · doi:10.3892/ijo.2015.3102 · Cited by 15 · see citing works
Differential gene regulation in DAPT-treated Hydra reveals candidate direct Notch signalling targets
Moneer, J., Siebert, S., Krebs, S., Cazet, J. F., Prexl, A., Pan, Q., Juliano, C. E., & Böttger, A. (2021) · Journal of Cell Science · doi:10.1242/jcs.258768 · Cited by 13 · see citing works
B., L. Q. I., Bartsch, N., Kouzel, I. U., Busengdal, H., Richards, G. S., Steinmetz, P. R. H., & Rentzsch, F. (2023) · Nature Communications · doi:10.1038/s41467-023-39789-4 · Cited by 13 · see citing works
Mashanov, V. S., Machado, D. J., Reid, R. W., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · BMC Genomics · doi:10.1186/s12864-022-08750-y · Cited by 12 · see citing works
Knabl, P., Schauer, A., Pomreinke, A. P., Zimmermann, B., Rogers, K. W., Čapek, D., Müller, P., & Genikhovich, G. (2024) · eLife · doi:10.7554/elife.80803 · Cited by 12 · see citing works
Perea-Atienza, E., Sprecher, S., & Martinez, P. (2017) · bioRxiv · doi:10.1186/s13227-018-0097-y · Cited by 9 · see citing works
Stone, M. C., Kothe, G. O., Rolls, M. M., & Jegla, T. J. (2020) · Journal of Experimental Biology · doi:10.1242/jeb.233197 · Cited by 12 · see citing works
Nematostella vectensis as a Model System
Al‐Shaer, L., Havrilak, J. A., & Layden, M. J. (2021) · CRC Press eBooks · doi:10.1201/9781003217503-7 · Cited by 12 · see citing works
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Evolution of glial cells: a non-bilaterian perspective
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Abdol, A. M., Röttinger, É., Jansson, F., & Kaandorp, J. A. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.06.004 · Cited by 6 · see citing works
Cell–cell communication in stem cells and cancer: Alone but in touch
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Havrilak, J. A., & Layden, M. J. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9732-9_2 · Cited by 3 · see citing works
Self-citationEchinoDB: an update to the web-based application for genomic and transcriptomic data on echinoderms
Mittal, V., Reid, R. W., Machado, D. J., Mashanov, V. S., & Janies, D. A. (2022) · BMC Genomic Data · doi:10.1186/s12863-022-01090-6 · Cited by 3 · see citing works
NvashA function reveals temporal differences in neural subtype generation in cnidarians
Havrilak, J. A., Cheng, M., Al‐Shaer, L., Leach, W. B., Yagodich, M., Faltine-Gonzalez, D. Z., & Layden, M. J. (2026) · Scientific Reports · doi:10.1038/s41598-026-41460-z · Cited by 2 · see citing works
Self-citationThe Notch pathway in Metazoa: a comparative analysis across cnidarians and beyond
Lövy, A., Kyslík, J., Picard‐Sánchez, A., Holzer, A. S., Krejčí, A., & Fiala, I. (2025) · EvoDevo · doi:10.1186/s13227-025-00246-6 · Cited by 2 · see citing works
Multiple Functions of Notch Signaling during Early Embryogenesis
López, S. L. (2022) · CRC Press eBooks · doi:10.1201/9781003050230-8 · Cited by 2 · see citing works
Notch expression during ctenophore development gives insight into its ancestral functionPreprint
Foster, B. M., Hugosson, F., Borba, C., Strother, J. A., & Martindale, M. Q. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.30.679519 · Cited by 2 · see citing works
Self-citationA draft genome assembly for the dart-poison frog Phyllobates terribilis
Márquez, R., Machado, D. J., Nouri, R., Gendreau, K. L., Janies, D. A., Saporito, R. A., Kronforst, M. R., & Grant, T. (2025) · Gigabyte · doi:10.46471/gigabyte.157 · Cited by 1 · see citing works
Vijayaraghavan, J., & Osborne, B. A. (2018) · Springer eBooks · doi:10.1007/978-1-4939-8859-4_2 · Cited by 1 · see citing works
Layden, M. J. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-7311-3_2
Self-citation(2017) · Elsevier eBooks · doi:10.1016/b978-0-12-812896-1.00040-4
Marine Shellfish Peptides and Bone Health
Du, M., Xu, Z., Cheng, S., Chang, Z., & Guo, R. (2025) · Springer eBooks · doi:10.1007/978-981-95-3937-6_5
Mittal, V., Reid, R. W., Machado, D. J., Mashanov, V. S., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.21385876
Mittal, V., Reid, R. W., Machado, D. J., Mashanov, V. S., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.21385879
Mashanov, V. S., Machado, D. J., Reid, R., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.20479599
Mashanov, V. S., Machado, D. J., Reid, R., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.20479608
Mashanov, V. S., Machado, D. J., Reid, R., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.20479590
Mittal, V., Reid, R. W., Machado, D. J., Mashanov, V. S., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.21385873
Mashanov, V. S., Machado, D. J., Reid, R., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.20479605
Kraus, J. E. M., Busengdal, H., Kraus, Y. A., Hausen, H., & Rentzsch, F. (2024) · Figshare · doi:10.6084/m9.figshare.26737911
Mashanov, V. S., Machado, D. J., Reid, R., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.20479602
Mashanov, V. S., Machado, D. J., Reid, R., Brouwer, C., Kofsky, J., & Janies, D. A. (2022) · Figshare · doi:10.6084/m9.figshare.20479596
- Authors
- Layden, M. J., & Martindale, M. Q.
- Affiliations
- Lehigh University (US)
- University of Florida (US)
- Corresponding author
- Martindale, Mark Q
- Venue
- EvoDevo
- Published
- 2014
- Volume
- 5
- Issue
- 1
- Pages
- 30
- ISSN
- 2041-9139 (ISSN-L)
- PMC
- PMC4335385
- OpenAlex
- W2100886237
- Cited by
- 68
- References
- 45
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 17 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 9
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- EvoDevo (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Florida Digital Collections (University of Florida) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM093116)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Marine Invertebrate Physiology and Ecology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Notch signaling, neuronal differentiation, Nematostella vectensis, Hes genes, Cnidaria, embryonic development
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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.
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