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Content archived on 2024-06-18

Specification of left-right symmetry and asymmetry in the nervous system

Objective

The generation of neurons during development from a fertilised egg requires a cascade of neuronal lineage-specific genes. This genetic cascade, and in particular the expression of proneural genes, is also required for efficient in vitro reprogramming of adult cells into neuronal cells for replacement therapies. Yet the upstream molecular events that directly regulate the expression of proneural transcription factors during embryogenesis remain ambiguous. The specification of neuronal lineages is further complicated by the fact that it needs to be coordinated across the left-right (L/R) axis. Our nervous system, like our body, is largely bilaterally symmetric yet both molecular and anatomical L/R asymmetries are also observed in the brain. Disruptions of bilateral and L/R asymmetric organisation in the human brain are frequently observed in Parkinson’s disease, schizophrenia and epilepsy. How symmetric and asymmetric neural determination programs are coordinated to establish a fully functional nervous system is poorly understood.

The first key aim of this proposal is to identify the cis-regulatory mechanisms and trans-acting factors that control both symmetric and asymmetric proneural gene expression in C. elegans using a combination of in vivo promoter analysis and reverse genetics. The second key aim of this proposal is to identify and characterise through forward genetic screens, 4D-lineage analysis and second-generation sequencing approaches, novel factors that act in two specific neuronal lineages to either (a) impart bilaterally symmetric neurogenesis or (b) regulate asymmetric neurogenesis. Since many principles of neural development are conserved from nematodes to vertebrates, defining in more detail the early steps of bilaterally symmetric and asymmetric neurogenesis in vivo in this genetic model system will allow us to generate neurons in vitro more efficiently and will advance our understanding and prevention of human neurological disease.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP7-PEOPLE-2013-CIG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-CIG - Support for training and career development of researcher (CIG)

Coordinator

UNIVERSITY COLLEGE LONDON
EU contribution
€ 100 000,00
Address
GOWER STREET
WC1E 6BT LONDON
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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