Objective
GABAergic interneurons play important roles in cortical function and provide the main source of inhibition to cortical microcircuits. Impaired interneuron function results in severe neurodevelopmental disorders such as schizophrenia, epilepsy and autism. Although recent studies have uncovered some of the molecular mechanisms underlying interneuron development, the intracellular components involved are still unknown. Our proposed work, aims to elucidate the role of specific signalling cascades during birth, migration and specification of interneurons, and thus shed light on the intracellular machinery that regulates their proper development.
Rac proteins integrate multiple extracellular signals and are required for many processes in diverse cell types, including cytoskeleton organization, vesicle trafficking, transcription, cell cycle progression, and apoptosis. We are interested in elucidating the roles of Rac1 and Rac3 specifically in MGE-derived interneurons, a population that comprises the majority of cortical interneurons. We have used conditional Rac1 deficient mice (specifically in the MGE) combined with Rac3 null mice and we found that 50% of MGE derived GABAergic interneurons fail to migrate and populate the cortex. MGE-derived interneurons missing both Rac proteins show an even more severe defect (80%). The aim of this proposal is to elucidate the mechanism of Rac1 and 3 action in interneuron development by assaying for: a) the polarity and the involvement of actin/microtubule dynamics in Rac deficient interneurons, b) the nature of the defect in interneuron progenitors as it concerns cell cycle behaviour c) the individual role of each of the two Rac proteins and the involvement of downstream effectors of the Rac pathway and d) the functional properties of interneurons.
The experiments designed combine molecular genetics, imaging, cellular and biochemical assays to reveal the mechanism of action of these intracellular mediators of interneuron development
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine neurology epilepsy
- natural sciences biological sciences molecular biology molecular genetics
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine psychiatry schizophrenia
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Topic(s)
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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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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2010-RG
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Funding Scheme
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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.
Coordinator
700 13 IRAKLEIO
Greece
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