Notch-signalling is required for head regeneration and tentacle patterning in Hydra
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Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals.
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Notch signalling in bud detachment and tentacle formation during regeneration are fundamentally different processes from neuronal differentiation.
“detachment of the bud and in tentacle formation during regeneration [66], thus, fundamentally different processes from neuronal differentiation.”
From Evolution of eumetazoan nervous systems: insights from cnidarians (2015) · cites this paper as [66]
In Hydra, chemical inhibition of Notch signalling suggests a role in boundary formation during detachment of the bud and in tentacle formation during regeneration, processes fundamentally different from neuronal differentiation.
“Notably, in hydra, chemical inhibition of Notch signalling suggests a role in boundary formation during detachment of the bud and in tentacle formation during regeneration [66], thus, fundamentally different processes from neuronal differentiation.”
From Evolution of eumetazoan nervous systems: insights from cnidarians (2015) · cites this paper as [66]
Cites
A theory of biological pattern formation
Gierer, A., & Meinhardt, H. (1972) · Kybernetik · doi:10.1007/bf00289234 · Cited by 3,158 · see citing works
Models of biological pattern formation
Meinhardt, H. (1982) · Cited by 1,829 · see citing works
Direct inhibition of the NOTCH transcription factor complex
Moellering, R. E., Cornejo, M., Davis, T. N., Bianco, C. D., Aster, J. C., Blacklow, S. C., Kung, A. L., Gilliland, D. G., Verdine, G. L., & Bradner, J. E. (2009) · Nature · doi:10.1038/nature08543 · Cited by 752 · see citing works
Cis-interactions between Notch and Delta generate mutually exclusive signalling states
Sprinzak, D., Lakhanpal, A., LeBon, L., Santat, L. A., Fontes, M. E., Anderson, G. A., García‐Ojalvo, J., & Elowitz, M. B. (2010) · Nature · doi:10.1038/nature08959 · Cited by 636 · see citing works
WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra
Hobmayer, B., Rentzsch, F., Kuhn, K., Happel, C. M., von Laue, C. C., Snyder, P., Rothbächer, U., & Holstein, T. W. (2000) · Nature · doi:10.1038/35025063 · Cited by 599 · see citing works
Kim, J., Sebring, A., Esch, J. J., Kraus, M. E., Vorwerk, K., Magee, J. A., & Carroll, S. B. (1996) · Nature · doi:10.1038/382133a0 · Cited by 488 · see citing works
Applications of a theory of biological pattern formation based on lateral inhibition
Meinhardt, H., & Gierer, A. (1974) · Journal of Cell Science · doi:10.1242/jcs.15.2.321 · Cited by 469 · see citing works
Defects in limb, craniofacial, and thymic development in Jagged2 mutant micePreprint
Jiang, R., Lan, Y., Chapman, H. D., Shawber, C. J., Norton, C. R., SERREZE, D. V., Weinmaster, G., & Gridley, T. (1998) · Genes & Development · doi:10.1101/gad.12.7.1046 · Cited by 422 · see citing works
Feed-back mechanisms affecting Notch activation at the dorsoventral boundary in the Drosophila wing
de Celis, J. F., & Bray, S. J. (1997) · Development · doi:10.1242/dev.124.17.3241 · Cited by 386 · see citing works
Takebayashi, K., Sasai, Y., Sakai, Y., Watanabe, T., Nakanishi, S., & Kageyama, R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37668-8 · Cited by 308 · see citing works
Multiple Wnts are involved in Hydra organizer formation and regeneration
Lengfeld, T., Watanabe, H., Simakov, O., Lindgens, D., Gee, L., Law, L. Y., Schmidt, H. A., Özbek, S., Bode, H. R., & Holstein, T. W. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.02.004 · Cited by 307 · see citing works
Formation of the head organizer in hydra involves the canonical Wnt pathway.
Broun, M., Gee, L., Reinhardt, B., & Bode, H. R. (2005) · Development · doi:10.1242/dev.01848 · Cited by 287 · see citing works
The production of new hydranths in Hydra by the insertion of small grafts
Browne, E. N. (1909) · Journal of Experimental Zoology · doi:10.1002/jez.1400070102 · Cited by 281 · 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
Hydra transplantation phenomena and the mechanism of Hydra head regeneration
MacWilliams, H. K. (1983) · Developmental Biology · doi:10.1016/0012-1606(83)90325-1 · Cited by 197 · see citing works
Meinhardt, H. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1138 · Cited by 165 · see citing works
Kunisch, M., Haenlin, M., & Campos‐Ortega, J. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.10139 · Cited by 159 · see citing works
Philipp, I., Aufschnaiter, R., Özbek, S., Pontasch, S., Jenewein, M., Watanabe, H., Rentzsch, F., Holstein, T. W., & Hobmayer, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812847106 · Cited by 152 · see citing works
cis-Inhibition of Notch by Endogenous Delta Biases the Outcome of Lateral Inhibition
Miller, A. C., Lyons, E. L., & Herman, T. G. (2009) · Current Biology · doi:10.1016/j.cub.2009.06.042 · Cited by 148 · see citing works
Pattern of epithelial cell cycling in hydra
Holstein, T. W., Hobmayer, E., & David, C. N. (1991) · Developmental Biology · doi:10.1016/0012-1606(91)90277-a · Cited by 146 · see citing works
Hydra transplantation phenomena and the mechanism of Hydra head regeneration
MacWilliams, H. K. (1983) · Developmental Biology · doi:10.1016/0012-1606(83)90324-x · Cited by 144 · see citing works
Grens, A., Mason, E., Marsh, J. L., & Bode, H. R. (1995) · Development · doi:10.1242/dev.121.12.4027 · Cited by 143 · see citing works
Budding inHydra attenuata:Bud stages and fate map
Otto, J. J., & Campbell, R. D. (1977) · Journal of Experimental Zoology · doi:10.1002/jez.1402000311 · Cited by 143 · see citing works
Autoregulatory and repressive inputs localize Hydra Wnt3 to the head organizer
Nakamura, Y., Tsiairis, C. D., Özbek, S., & Holstein, T. W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018109108 · Cited by 134 · see citing works
Leontovich, A. A., Zhang, J., Shimokawa, K., Nagase, H., & Sarras, M. P. (2000) · Development · doi:10.1242/dev.127.4.907 · Cited by 128 · see citing works
Characterization of the head organizer in hydra
Broun, M., & Bode, H. R. (2002) · Development · doi:10.1242/dev.129.4.875 · Cited by 127 · see citing works
β-catenin plays a central role in setting up the head organizer in hydra
Gee, L., Hartig, J. V., Law, L. Y., Wittlieb, J., Khalturin, K., Bosch, T. C. G., & Bode, H. R. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2009.12.036 · Cited by 105 · see citing works
HyBMP5-8b , a BMP5-8 orthologue, acts during axial patterning and tentacle formation in hydra
Reinhardt, B., Broun, M., Blitz, I. L., & Bode, H. R. (2003) · Developmental Biology · doi:10.1016/j.ydbio.2003.10.031 · Cited by 101 · see citing works
The 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
Self-citationNotch signaling, the segmentation clock, and the patterning of vertebrate somites
Lewis, J. H., Hanisch, A., & Holder, M. V. (2009) · Journal of Biology · doi:10.1186/jbiol145 · Cited by 96 · see citing works
HyAlx, an aristaless-related gene, is involved in tentacle formation in hydra
Smith, K. M., Gee, L., & Bode, H. R. (2000) · Development · doi:10.1242/dev.127.22.4743 · Cited by 95 · see citing works
Broun, M., Sokol, S. Y., & Bode, H. R. (1999) · Development · doi:10.1242/dev.126.23.5245 · Cited by 91 · see citing works
Positional information and pattern regulation in regeneration of hydra.
Wolpert, L., Hicklin, J., & Hornbruch, A. (1971) · PubMed · Cited by 88 · see citing works
Modeling pattern formation in hydra: a route to understanding essential steps in development
Meinhardt, H. (2012) · The International Journal of Developmental Biology · doi:10.1387/ijdb.113483hm · Cited by 77 · see citing works
Differentiation pathways of ectodermal epithelial cells in hydra
DUBEL, S. J., Hoffmeister, S. A. H., & Schaller, H. C. (1987) · Differentiation · doi:10.1111/j.1432-0436.1987.tb00167.x · Cited by 76 · see citing works
The pattern of transcription of the neurogenic gene Delta of Drosophila melanogaster
Haenlin, M., Kramatschek, B., & Campos‐Ortega, J. A. (1990) · Development · doi:10.1242/dev.110.3.905 · Cited by 73 · see citing works
Development of the two-part pattern during regeneration of the head in hydra
Bode, P. M., Awad, T. A., Koizumi, O., Nakashima, Y., Grimmelikhuijzen, C. J. P., & Bode, H. R. (1988) · Development · doi:10.1242/dev.102.1.223 · Cited by 67 · see citing works
Campos‐Ortega, J. A., & Knust, E. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15538.x · Cited by 61 · see citing works
Takano, J., & Sugiyama, T. (1983) · Development · doi:10.1242/dev.78.1.141 · Cited by 60 · see citing works
Sudhop, S., Coulier, F., Bieller, A., Vogt, A., Hotz, T., & Hassel, M. (2004) · Development · doi:10.1242/dev.01267 · Cited by 59 · see citing works
Notch signalling defines critical boundary during budding in Hydra
Münder, S., Käsbauer, T., Prexl, A., et al. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.05.517 · Cited by 54 · see citing works
Self-citationAnd Lophotrochozoa makes three: Notch/Hes signaling in annelid segmentation
Rivera, A. S., & Weisblat, D. A. (2008) · Development Genes and Evolution · doi:10.1007/s00427-008-0264-6 · Cited by 47 · see citing works
Cell movements controlled by the Notch signalling cascade during foregut development in Drosophila
Fuß, B., Josten, F., Feix, M., et al. (2004) · Development · doi:10.1242/dev.01057 · Cited by 45 · see citing works
GFP expression in Hydra: lessons from the particle gun
Böttger, A., Alexandrova, O., Cikala, M., Schade, M., Herold, M., & David, C. N. (2002) · Development Genes and Evolution · doi:10.1007/s00427-002-0245-0 · Cited by 44 · see citing works
Self-citationHydra, a model system to trace the emergence of boundaries in developing eumetazoans
Böttger, A., & Hassel, M. (2012) · The International Journal of Developmental Biology · doi:10.1387/ijdb.113454ab · Cited by 27 · see citing works
Self-citationPrexl, A., Münder, S., Loy, B., Kremmer, E., Tischer, S., & Böttger, A. (2011) · BMC Cell Biology · doi:10.1186/1471-2121-12-38 · Cited by 15 · see citing works
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Evolution 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
Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation
Layden, M. J., & Martindale, M. Q. (2014) · EvoDevo · doi:10.1186/2041-9139-5-30 · Cited by 68 · see citing works
- Authors
- Münder, S., Tischer, S., Grundhuber, M., Büchels, N., Bruckmeier, N., Eckert, S., Seefeldt, C. A., Prexl, A., Käsbauer, T., & Böttger, A.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Böttger, Angelika
- ORCID
- Böttger, Angelika
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 383
- Issue
- 1
- Pages
- 146-157
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W1975337787
- Cited by
- 51
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 8 · 2023: 1 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 9 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- DFG (BO1748-5)
- Topics
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Marine Invertebrate Physiology and Ecology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
- Keywords
- Notch signaling, Hydra, head regeneration, hypostome, lateral inhibition, Wnt signaling, β-catenin, body plan evolution, axial patterning
- MeSH terms
- Animals, Bromodeoxyuridine, Dipeptides, Extremities, Head, Hydra, Regeneration, Signal Transduction, In Situ Hybridization, DNA Primers, Microscopy, Confocal, Receptors, Notch
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