Award details

Evolutionary mechanisms controlling brain size and complexity

Reference	BB/S001530/1
Principal Investigator / Supervisor	Professor Corinne Houart
Co-Investigators / Co-Supervisors
Institution	King's College London
Department	Developmental Neurobiology
Funding type	Research
Value (£)	687,921
Status	Completed
Type	Research Grant
Start date	01/10/2018
End date	30/09/2021
Duration	36 months

Abstract

All vertebrate brains, from fish to human, are formed of the same regions (forebrain, midbrain and hindbrain) but their relative size and complexity vary tremendously across evolution. The telencephalon and the cerebellum are the two areas showing the biggest variation, reaching the highest complexity and being the most common target in human neurodevelopmental and neurodegenerative disorders. It is therefore of crucial importance to understand how this complexity is reached during development and what are the genetic driving elements ensuring formation of a normal complex brain such as ours. Our lab is an international leader in early brain development, having unveiled the signalling mechanism establishing the telencephalic territory inside the forming brain. We very recently found that changes in timing of signalling inside the anterior neural plate modify the size and the complexity of the developing telencephalon. Here, we propose to identify the cellular and molecular mechanisms controlling timing of signalling and understand the complexity-generating progression triggered by this temporal change. As the events controlling brain size and complexity are the prime targets for disorders, identifying them will lead to new understanding of disorder mechanisms and to new candidate disorder-causing genes

Summary

All vertebrate brains, from fish to human, are formed of the same regions (forebrain, midbrain and hindbrain) but the relative size and complexity of each of these vary tremendously across evolution. The telencephalon (part of the forebrain forming our brain hemispheres) and the cerebellum (part of the hindbrain) are the two areas showing the biggest variation, reaching the highest complexity and being the most common target in human developmental and neurodegenerative disorders. It is therefore of crucial importance to understand how this complexity is reached during development and what are the initial genetic driving elements ensuring formation of a normal complex brain such as ours. Our lab is an international leader in early brain development, having unveiled the signalling mechanism establishing the telencephalic territory inside the forming brain. We very recently found that changes in timing of signalling inside the very early brain tissue (called the neural plate) modify the size and the complexity of the telencephalon. Here, we propose to identify the cellular and molecular mechanisms controlling timing of signalling and understand the complexity-generating progression triggered by this temporal change. As the events controlling brain size and complexity are the prime targets for disorders, identifying them will lead to new understanding of disorder mechanisms and to new candidate disorder-causing genes.

Impact Summary

1. Academic impact The expected beneficiaries of this research proposal are mainly the scientists and clinicians in the fields of cell biology, developmental neurobiology and neurodevelopmental disorders. 2. From basic research to clinic The beneficiaries are clinicians working on neurodisorders involving signalling events in their pathology as this project will lead to identification of novel molecules and molecular mechanisms involved in these processes. We will engage with international clinicians specialized in these pathologies by participating to clinical symposia (ASD and microcephaly). 3. Application and exploitation: Any commercial potential of our discoveries will be discussed with KCL enterprise. Potential commercial outcome may stem from this proposal but will require further research development before any commercial venture can be envisaged. However, development of research projects with the industry may well stem from the proposed research. 4. Communications and engagement: The lead applicant is communicating her results through public lectures in school and public events organised by various organisations. She also teaches at and direct international courses and organises international workshops (eg. EMBO. MBL). Our Centre for Neurodevelopmental Disorders website has a dedicated page for public communications of research output that will be used by the applicant. The findings will be shared with the public (see beneficiaries). All peer-reviewed articles will be published in Open Access format and findings will be explained in the form of public lectures and illustrations/3D model made for public science exhibitions. The lead applicant has contacts with the BBC to explore possibilities of a new form of public communication of our results promoting at the same time the impact of basic research on Health and the involvement of women in research advances.

Committee	Research Committee C (Genes, development and STEM approaches to biology)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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