Evolution of the vertebrate inner ear: a gene network approach

Lead Research Organisation: University of Oxford
Department Name: Biology


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Technical Summary

Evolution of complex organs is thought to be driven by changes in the gene regulatory networks (GRNs) that control development: recruiting new components into ancestral GRNs allows the emergence of new cell types and cell behaviours. Alterations in the non-coding regulatory regions are hypothesised to drive such changes in network architecture. Here, we will systematically test this hypothesis to provide mechanistic insight into evolution of a complex sense organ, the ear, from basal chordates to higher vertebrates.

We have recently established the GRN that controls inner ear commitment in a higher vertebrate, the chick, including the regulatory regions that integrate information. Like in chick, the ear in a lower vertebrate, the lamprey, arises from the otic placode, while the proto-placodal domain (PPD) in a lower chordate, Ciona, generates mechanoreceptor cells, like those in the vertebrate ear.

First, we will establish which GRN components are present in the lamprey placode and the Ciona PPD using comparative gene expression.
Second, we will identify the regulatory regions that control ear and PPD gene expression in lamprey and Ciona, respectively, using bioinformatics and ATACseq, and test their activity in vivo. This will complement our chick enhancer database providing a framework for studying how the GRN changed during evolution.
Third, we will explore which regulatory inputs into ear and PPD genes are conserved and which diverge. We will determine the minimal elements required to drive reporters in the vertebrate ear, test their in vivo activity across all three species, and analyse changes in enhancer motifs. We will identify factors missing in the ancestral network, and attempt to engineer a vertebrate-like enhancer from ancestral Ciona enhancers.

Planned Impact

The proposed project is multidisciplinary combining biology, molecular and computational approaches and addresses the fundamental question of how changes in developmental mechanisms allowed the evolution of complex organs like the ear. It cuts across several BBSRC priority areas: data driven biology, 3Rs in research using animals, systems approaches to biosciences and technology development in biosciences.

There are various academic beneficiaries (see above) because the project addresses a basic biology question: how changes in the regulatory landscape led to the emergence of complex organs from lower chordates to higher vertebrates. These include researchers in the field of neuroscience and auditory biology, developmental, stem cell and systems biology, and evolutionary biology.

Our data will be published in scientific journals, at conferences and through teaching and outreach events, with all genomics and experimental data being made publicly available. Therefore, these benefits will occur during the course of the project or shortly thereafter. In the proposed project we will only investigate some simple scenarios for changes in GRN architecture across evolution. However, our data will provide a rich resource for further studies and generate new testable hypotheses that can be explored by the research community in future.

The project also has benefits beyond academia, although some may take longer to bear fruit. In particular, Evolution as a topic arouses a lot of interest in the general public and it is therefore easy to convey through public lectures, science fairs and engagement activities with pupils and students. Beneficiaries beyond academia will include
- Training of highly skilled researchers in interdisciplinary research; this training will not only equip the PDRAs with skills for a career in science, but also with many transferable skills such as organisation, critical thinking, problem solving, modelling complex scenarios, cross-disciplinary interactions and many more. This will therefore contribute to strengthening the UK economy by providing highly skilled personnel for the academic or private sector.
- Our new collaboration with an artist, Tabatha Andrews, will bring a new perspective into scientific thinking and approach to science. Tabatha's interest lies in sensory perception and how changes affect humans. We have planned a project entitled 'Knowing, Remembering, Listening: How do cells and people know who they are?'. This involves lab visits, a workshop and exhibit at King's Science Gallery and focuses on the concept of identity, memory and communication with respect to cells and humans. This will particularly benefit the personal and scientific development of the PDRA, and shape her/his ability for public engagement and science communication in the future. This is also an important training aspect for the PDRA, but will go beyond training to involve other scientists and general public alike.
- The project will also have a focus on computational approaches; this will contribute to alleviating current shortage in bioinformatics skills by attracting new talent into this area.
- Enhancing the international reputation of UK science will increase international collaborations. In particular, our collaboration with M. Bronner at Caltech, Pasadena will strengthen international links and enhance our global influence.
- Enthusing young people to take up a career in science; our outreach activities specifically target young individuals as future talents (school pupils in short lab projects, school visits, KCL Science Gallery targeting the local young population, collaboration with an artist to create exhibits and run workshops). Evolutionary questions are excellent to capture the imagination of the general public, in particular children and teenagers. This will support the UKs ambition for strong science underpinning growth of the economy, entrepreneurial activities and industrial development.


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