Molecular evolution of cell adhesion and polarity

Establishment of organized tissues represented a major achievement in animal evolution. One of the most significant tissue specializations was the evolution of true epithelia formed by a single layer of polarized cells. This most likely admitted morphogenetic movements and a considerably improved control of the inside of the organisms and resulted in the radiation of more complex body plans and differentiated tissues like muscles and the nervous system. Formation of tissue layers is a basic organizing principle in normal embryogenesis in higher metazoans. Destabilization of epithelial organization in tumors contributes to malignant transformation. Over the past few years, intensive analysis in the model organisms Caenorhabditis, Drosophila, Xenopus, and mouse has uncovered highly conserved cell membrane-associated protein complexes and signaling pathways regulating formation, stability, and movement of epithelia. Despite their importance, the evolutionary origin of these mechanisms in early multicellular animals is unclear. In this proposal, we want to investigate molecular mechanisms of tissue formation in the simple, diploblastic metazoan Hydra. Reaggregation of Hydra polyps from single cell suspensions offers a two cell type in vitro system to study the establishment of cell adhesion, cell polarity, and cell signaling. Based on our previous work on cell sorting and the characterization of a cadherin-catenin adhesion complex in Hydra, we want to tackle three specific problems in this project: (1) Systematic screening of genes whose expression is regulated during early aggregation. (2) Analysis of structure and function of the Hydra cadherin-catenin complex. (3) Characterization of planar cell polarity genes in Hydra. Analysis of the expression profile during early aggregation will provide a more detailed understanding of the intercellular communication in small cell aggregates setting up adhesive contacts, polarity, and their ability to act as signaling centers. By learning how the Hydra cadherin-catenin complex is connected with the cytoskeleton and which planar cell polarity genes act in the Hydra epithelium, we will add to an understanding of the original establishment of stable cell-cell contacts and cellular polarity in the earliest organized tissue layers.

Establishment of organized tissues represented a major achievement in animal evolution. One of the most significant tissue specializations was the evolution of true epithelia formed by a single layer of polarized cells. This most likely admitted morphogenetic movements and a considerably improved control of the inside of the organisms and resulted in the radiation of more complex body plans and differentiated tissues like muscles and the nervous system. Formation of tissue layers is a basic organizing principle in normal embryogenesis in higher metazoans. Destabilization of epithelial organization in tumors contributes to malignant transformation. Over the past few years, intensive analysis in the model organisms Caenorhabditis, Drosophila, Xenopus, and mouse has uncovered highly conserved cell membrane-associated protein complexes and signaling pathways regulating formation, stability, and movement of epithelia. Despite their importance, the evolutionary origin of these mechanisms in early multicellular animals is unclear. In this proposal, we want to investigate molecular mechanisms of tissue formation in the simple, diploblastic metazoan Hydra. Reaggregation of Hydra polyps from single cell suspensions offers a two cell type in vitro system to study the establishment of cell adhesion, cell polarity, and cell signaling. Based on our previous work on cell sorting and the characterization of a cadherin-catenin adhesion complex in Hydra, we want to tackle three specific problems in this project: 1. Systematic screening of genes whose expression is regulated during early aggregation. 2. Analysis of structure and function of the Hydra cadherin-catenin complex. 3. Characterization of planar cell polarity genes in Hydra. Analysis of the expression profile during early aggregation will provide a more detailed understanding of the intercellular communication in small cell aggregates setting up adhesive contacts, polarity, and their ability to act as signaling centers. By learning how the Hydra cadherin-catenin complex is connected with the cytoskeleton and which planar cell polarity genes act in the Hydra epithelium, we will add to an understanding of the original establishment of stable cell-cell contacts and cellular polarity in the earliest organized tissue layers.