The molecular mechanism of tissue boundary formation in animals

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Hydra is a member of the ancient phylum Cnidaria. Genome sequencing carried out for Hydra and other pre-bilaterian animals has revealed that the major signalling pathways governing embryonal development and cellular homeostasis in mammals, including Notch signalling, were already present in these early metazoans. Dysregulation of Notch-signalling leads to cancer and degenerative disease. In Hydra, blocking Notch-signalling inflicts a differentiation block in the interstitial stem cell lineage and causes severe disturbances of tissue patterning. Three signalling pathways have previously been shown to regulate the head to foot patterning in Hydra. These include the Wnt-pathway, BMP- and FGF-signalling. They are regulated by soluble ligands, which may establish gradients of signalling activity. In contrast, Notch signalling depends on direct cell contact and it causes a sharp switch in signalling states between two neighbouring cells. This allows the creation of boundaries between cells adapting opposite fates, e.g proliferating cells in the tentacle zone and differentiating cells in the tentacles. Hydra with its relatively simple body plan and its unique morphological plasticity in adult animals allows to dissect the molecular principles of integrating diffusible and contact dependent signals for shaping tissue patterns in animals. This is the long-term aim of this proposal. In the first period we want to identify Notch-target genes with the help of a transcriptome study and investigate their expression patterns. We may discover novel Notch-targets in Hydra with homologs in mammals. These could be relevant for developing new drug targets to combat Notch-dysfunction in humans. In addition, with the help of a Notch-signalling reporter, we want to detect the cells where Notch-signals are received during Hydra head regeneration and tentacle patterning. Integrating this information with semi-quantitative expression studies of Notch-ligand and receptor will explain how Notch cell-contact dependent signalling events are positioned by upstream factors to achieve the observed precision in patterning body structures in Hydra.