Evolution of the vertebrate inner ear: a gene network approach

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The eye, nose and ear constantly provide signals from the environment that allow us to communicate with each other, to react to changes by adjusting our behaviour and to navigate the world throughout daily life. In all vertebrates, including humans, these sense organs are very complex and are concentrated in the head, while sensory structures in lower, non-vertebrate animals of the same phylum are much less sophisticated and generally consist of cells scattered across the body. It is therefore thought that a key feature that made the evolution of vertebrates possible is the emergence of sense organs: they allowed animals to move from a passive to a more active life style including hunting for food and escaping predators, and therefore to explore new habitats. Thus, understanding the evolution of sense organs is an important piece in the puzzle of understanding human evolution.Surprisingly, we know very little about the mechanisms that drove the formation of sophisticated sense organs, and this proposal addresses this question using the ear as a model organ. We have recently established the 'wiring diagram' that controls early ear development in a higher vertebrate, the chick, using modern molecular techniques. We have identified some of the key drivers that push stem cells towards ear identity, established how they act in a molecular hierarchy, and how these events are controlled by so called 'regulatory regions' in the DNA. With this blueprint for vertebrate ear formation, we can now ask: what was the ancestral 'wiring diagram' in a basic vertebrate, the lamprey, and the closest vertebrate relative, the sea squirt, and what are the molecular mechanisms that allowed the emergence of sophisticated sense organs? We will establish which of the components that we have identified in the chick are also present in the lamprey ear and in the 'ancestral ear' of the sea squirt. Molecules present in all three species will be part of the most ancient wiring diagram, while those present in lamprey and chick will characterise the vertebrate lineage.We have already characterised the regulatory regions that control the expression of ear genes in chick. Our hypothesis is that changes in these regulatory elements allowed the recruitment of new genes into the ancient ear wiring diagram and thus allowed evolution of sophisticated vertebrate ears. To test this hypothesis we will use bioinformatics and molecular approaches to identify similar regions in lamprey and the sea squirt, assess their activity across all three species and use molecular tools to characterise the most crucial parts of these elements. Comparison across species will allow us to define the most ancient molecular network in the closest relative of vertebrates, as well as the molecular events that increased complexity of the wiring diagram for ear formation during evolution. This project will therefore make an important contribution to our understanding of vertebrate evolution, in particular highlighting the events that allowed the emergences of sophisticated structures that define the function of human organs and are key to define human behaviour.