Genetic analysis of a novel family of repulsive guidance cues acting through Unc5 receptors

Objective

One of the most challenging problems in neurobiology is to understand the mechanisms that mediate the formation of a functional neuronal network. Despite the identification of several molecules that regulate axon guidance and cell migration, it is unclear how these factors can specify a large number of connections in the nervous system.
The present project aims to study the role and mechanism of action of the Fibronectin Leucine-Rich Transmembrane (FLRT) family protein in axon guidance and cell migration during mouse central nervous system (CNS) development. The proposed fellow intends to tackle this problem using a multidisciplinary approach including conditional mouse mutant mice lacking either specific FLRT or Unc5 proteins, cell based functional assays using neurons derived from mutant mice, and molecular and biochemical assays to identify signalling pathways activated by FLRTs. Recent unpublished results from the proposed host institution, the Department of Molecular Neurobiology (Dr. Klein) at Max Planck Institute of Neurobiology, indicate that shed ectodomains of FLRTs can function as long-range guidance cues for cortical neurons in vitro and in vivo. FLRTs exert their functions by binding to Unc5 receptors. Moreover, FLRTs may also act as cell autonomous signaling receptors. Thus, FLRT proteins have the potential to engage in bi-directional signaling (‘forward’ via Unc5 receptors and ‘reverse’ via their own intracellular domain), an original and innovative concept which Dr. Klein previously pioneered in the ephrin/Eph field. Should the hypothesis of the proposed research be correct, the findings will undoubtedly represent an advance in the state of art in the neurobiology area, and also may shed light on certain neural developmental disorders.
The proposed fellow will highly benefit from the challenging research environment and supervision of a renowned scientist, which will offer him promising perspectives for his further research career in Europe.

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.

• natural sciences biological sciences neurobiology
• natural sciences biological sciences biochemistry biomolecules proteins
• natural sciences biological sciences molecular biology molecular neuroscience

Programme(s)

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• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

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.

• FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2010-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator