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CDH2_NEUROMIGRATION

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The cytoskeleton and Cadherin 2 are tightly linked to coordinate nucleokinesis i...

The cytoskeleton and Cadherin 2 are tightly linked to coordinate nucleokinesis in migrating neurons The cerebellum coordinates the body’s movements. It consists of distinct layers of neuronal populations, but during embryonic development, these neurons are generated distantly from their final locations. In zebrafish, this means... ver más

31/01/2017

TECHNISCHE UNIVERS...

162K€

Presupuesto del proyecto: 162K€

Líder del proyecto

TECHNISCHE UNIVERSITAET BRAUNSCHWEIG 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 2017-01-31 No tenemos la información de la convocatoria

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1 Participantes

TECHNISCHE UNIVERSITAET BRAU...

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Líder del proyecto

TECHNISCHE UNIVERSITAET BRAUNSCHWEIG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 162K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The cerebellum coordinates the body’s movements. It consists of distinct layers of neuronal populations, but during embryonic development, these neurons are generated distantly from their final locations. In zebrafish, this means that cerebellar neurons have to migrate from the upper rhombic lip to the midbrain-hindbrain boundary and further. While descriptions of the migratory pathways for the different neuronal populations have become available in recent years, fundamental questions of this process are still unanswered. Firstly, we currently do not know how guidance of these cells is achieved and translated into directional motility. Activity could be a guiding cue, as it creates intracellular Ca2+-transients which determine directionality in cerebellar neurons. Similarly, depletion of Cadherin-2, a cell-adhesion molecule and key regulator of cell migration, leads to loss of directionality. If activity works through Cadherin-2 to guide cells, it would present a novel way of transmitting information from outside to the inside of cells. We will test this notion using the latest genetic tools. Secondly, Cadherin-2 influences centrosome-positioning, yet we do not know the molecular mechanism of this. IQGAP1 could be the link between Caherin-2 and the microtubules, but this remains to be proven. Thirdly, in order to generate movement of the cells, the forces from the cytoskeleton need to be transmitted to the nucleus. Two models for such mechanisms are being debated, and we will test both in migrating cells in vivo. To address these questions, we will use an interdisciplinary approach combining techniques and knowledge from cell biology, developmental biology and genetics with advanced in vivo time-lapse imaging. Understanding how the cells’ migration is guided and regulated will improve the fundamental knowledge for the development of therapies for patients suffering from brain injuries or lissencephalies, and create a unique focus of cerebellar research in Europe.

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