Developmental Pathways in early metazoans
Zusammenfassung der Projektergebnisse
Porifera, placozoa, ctenophores and cnidarians were the first multicellular animals that appeared on earth. In going from a single-celled condition to multicellularity, a number of cellular functions had to be greatly changed and even newly invented. This especially concerns intercellular communication. Thus, new signalling pathways evolved along with multi-cellular animals. These are conserved from these ancient phyla to humans and they govern embryonic development, when a new organism develops from a fertilised egg. Disturbance of these signalling pathways leads to human disease, including proliferative and degenerative diseases and cancer. We have investigated the function of Notch-signalling in the cnidarian "Hydra". The unifying hallmark of Notch-function in animal development is to allow differentiation events to occur at precise positions and times. In many cases Notch-signalling facilitates fate switches between two adjacent cells, thereby promoting boundary formation. As a result of research carried out we have demonstrated high conservation of known components of canonical Notch-signalling including protein sequences of Notch- receptor and ligand, the target gene "Hes" and the mode of signalling through regulated intramembrane proteolysis. Using two different Notch-inhibitors we showed that in "Hydra" Notch signalling is important for interstitial stem cell differentiation, budding and head regeneration. Continuous inhibition of Notch-signalling leads to multi-headed animals because buds remain connected with the parent animals. This is due to a failure in forming a sharp boundary between bud and mother tissue, which appears to be required for the bud to make a foot. In addition, the tentacle boundaries in adult animals require Notch-signalling. This has implications for "Hydra" head regeneration. When Notch-signalling is blocked during this process, a new head organiser cannot be formed and regeneration fails. Interestingly, tentacle tissue is made nevertheless, leading to aberrant head structures lacking the hypostome. Our results will help to understand the evolution of intercellular communication in animals and answer questions as to how a small number of signalling pathways regulates development of animals with incredibly diverse of body plans and why some animals can exploit these pathways to regenerate missing body parts and others cannot. They will contribute to a generally better understanding of the molecular logic of Notch-signalling and this may have implications for finding drug targets to develop new treatments for human disease.
Projektbezogene Publikationen (Auswahl)
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(2007): The Notch signalling pathway in the cnidarian Hydra, Developmental Biology 303(1):376-90
Tina Käsbauer, Par Towb, Olga Alexandrova, Charles N. David, Ekaterina Dall’Armi, Andrea Staudigl, Beate Stiening, and Angelika Böttger
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(2010). Notch signalling defines critical boundary during budding in Hydra, Developmental Biology, 344(1):331-45
Münder, S., Käsbauer, T., Prexl, A., Aufschnaiter, R., Zhang, X., Towb, P. and Böttger, A.
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(2010). The Dynamic Genome of Hydra, Nature 464 (7288):592-6
Chapman, JA, Kikness, EF, Simiakov, O, Böttger, A, Rokshar, DS, Steele, RE
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(2011). The putative Notch Ligand HyJagged is a transmembrane protein present in all cell types of adult hydra and upregulated at the boundary between bud and parent: BMC Cell Biology 12, 38
Prexl, A., Münder, S., Loy, B., Kremmer, E., Tischer, S, and Böttger, A.
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(2012) Hydra, a model system to trace the emergence of boundaries in developing eumetazoans): Int J. Dev. Biol 56 (6-8); 583-591
Angelika Böttger, Monika Hassel
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(2013). Eph receptors and ephrin class B ligands are expressed at tissue boundaries in Hydra vulgaris, Int. J. Dev.Biol, 57(9-10): 759-65
Tischer, S, Reineck, M, Söding, J, Münder, S, Böttger, A
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(2013). Notch-signalling is required for head regeneration and tentacle patterning in Hydra. Developmental Biology, 383, 146-157
Münder, S., Tischer, S., Grundhuber, M., Buchels, N., Bruckmeier, N., Eckert, S., Seefeldt, C.A., Prexl, A., Kasbauer, T., Böttger, A.
