RACS

The role of Rac1 and Rac3 in cortical interneuron development

Coordinatore	FOUNDATION FOR RESEARCH AND TECHNOLOGY HELLAS    more  Organization address address: N PLASTIRA STR 100 city: HERAKLION postcode: 70013 contact info Titolo: Ms. Nome: Zinovia Cognome: Papatheodorou Email: send email Telefono: +30 2810 391522 Fax: +30 2810 391555
Nazionalità Coordinatore	Greece [EL]
Totale costo	45˙000 €
EC contributo	45˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-RG
Funding Scheme	MC-ERG
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-10-01   -   2013-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FOUNDATION FOR RESEARCH AND TECHNOLOGY HELLAS  Organization address address: N PLASTIRA STR 100 city: HERAKLION postcode: 70013 contact info Titolo: Ms. Nome: Zinovia Cognome: Papatheodorou Email: send email Telefono: +30 2810 391522 Fax: +30 2810 391555	EL (HERAKLION)	coordinator	45˙000.00

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 Obiettivo del progetto (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'