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MESSENGER CODES

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Dynamics of second messengers in axon guidance decrypting the codes

The mature nervous system is an intricate network in which neurons are connected to specific partners. The construction of the network requires directed growth of axons towards their appropriate targets during development and duri... ver más

30/09/2011

INSERM

239K€

Presupuesto del proyecto: 239K€

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2011-09-30 No tenemos la información de la convocatoria

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Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 239K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The mature nervous system is an intricate network in which neurons are connected to specific partners. The construction of the network requires directed growth of axons towards their appropriate targets during development and during neuronal regeneration after a lesion. Axons must navigate through a complex environment where they are guided by a combination of attractive and repulsive molecules. Cellular second messengers, particularly calcium and cyclic nucleotides – cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) – are critical for responses to guidance molecules and axonal pathfinding. Recently, the temporal structure of calcium signals has been shown to have a key role in regulating growth cone behaviors, but the temporal components of cAMP and cGMP signals are largely unknown. The present project proposes to investigate the involvement of second messengers during the midline crossing of spinal commissural axons in vivo. We will first identify the crucial second messengers for the guidance of those axons in the Xenopus spinal cord in vivo. Second, we will use newly improved cyclic nucleotide FRET probes and fluorescent calcium sensors to determine the temporal dynamics of cAMP, cGMP and calcium signaling (the frequency of transients and sustained variations in their intracellular concentrations) in vivo in the growth cones of spinal commissural interneurons. We will then investigate the respective roles of temporally restricted and sustained variations of second messengers in the guidance of commissural axons in vivo, by imposing different frequencies of transient or sustained perturbations of cAMP, cGMP and calcium. Finally, we will investigate the interdependence of these signaling pathways by imaging one second messengers while manipulating another. These studies will substantially advance our understanding of signaling necessary for axonal pathfinding by spinal cord neurons.

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