How do new levels of biological organization arise? Vertebrate organs are composed of interdependent cell types from evolutionarily distinct families that form stable, integrated tissue units. This project addresses the origin of such units using vertebrate digestive organs as a model. My empirical work shows that cell types homologous to vertebrate hepatic and pancreatic parenchymal cells are present in invertebrate chordates (amphioxus and Ciona), organized into coherent spatial clusters, but assembled with non-homologous supportive cell types, raising questions about how tissue units originate and how their homology should be assessed. At the KLI, I propose to use these findings to (1) identify the metabolic interdependencies that enable cell types to become integrated into supra-cellular units, and (2) develop homology criteria that accommodate discordant evolutionary histories at different levels of organization, in collaboration with KLI External Faculty Drs. Gunter Wagner and Mihaela Pavlicev.