SYNAXON · Molecular mechanisms controlling axonal development and synapse formation
6РП — Действия „Мария Кюри“
- Период
- 2005-04-01 → 2007-03-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите.
Накратко на български
Молекулярните механизми, които контролират изграждането и подрязването на невронните връзки, се изучават чрез протеина FAK и семафорин 3A. Разбирането на тези процеси помага при изясняването на невродегенеративните заболявания и начина, по който мозъкът се променя.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - SYNAXON (Molecular mechanisms controlling axonal development and synapse formation)
During initial brain wiring, neurons generate more connections than ultimately survive; some of these connections are pruned, whereas others are stabilised to constitute a mature neuronal network. Relatively little is known about the molecular mechanisms that control axonal branch formation and stabilisation. Using frontier technology, we are now able to generate mice lacking a gene of interest in a tissue or cell-type specific-manner to study protein function. We have demonstrated first, that the protein kinase FAK is needed for healthy and dynamic axon establishment, additionally, distribution and amount of the cytoskeleton (the scaffold of the neuron) depends on the presence of FAK protein. Second, we have shown that the extracellular cue, semaphorin 3A is mediating FAK activation to control axonal pruning, an event necessary to adjust the final neuronal network. Some of the insights of this investigation will probably be applicable for understanding not just the initial development of neural connections but also normal plastic rearrangements of neural connections occurring in the healthy and pathologic brains. Understanding the mechanisms that underlie the formation of neural circuits is not only a major biological challenge, but also has important implications in disease. For example, there are many common cellular and molecular mechanisms between the processes of pruning by degeneration, as it occurs normally during development, and neuronal degeneration and cell dead in neurodegenerative disorders. Therefore, unravelling the molecular machinery controlling the process of pruning during development is likely to offer new venues to understanding neuropathological states.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
During nervous system development, neurons generate more axonal processes than ultimately survive; some of these axonal branches are pruned, whereas others are stabilized to constitute a mature neuronal network. Relatively little is known about the molecular mechanisms that control axonal branch formation and stabilization. Functional analysis of diverse molecules during development has been carried out by means of the generation of regular mutant mice. However, the early mortality of these mutants has prevented their analysis during postnatal development, particularly in the central nervous system. To overcome this problem, conditional-mutant mice using the Cre/LoxP recombination system has been generated.Using this technology, the production of mice lacking a gene of interest in a tissue or cell-type specific-manner has been possible. In our previous studies, we have used conditional-mutants to investigate the function of the focal adhesion kinase, FAK. We have demonstrated that FAK is a positive cue for a xonal elongation and a negative cue for axonal branching, and consequently synapse establishment. The aim of this proposal is to characterize the molecular mechanisms by which FAK is controlling axonal development and synapse formation.Using cell-specific ablation in cortical cultures we propose to accomplish three fundamental goals:(1) to determine the role of local FAK in axonal elongation and branching in vivo,(2) to establish the downstream pathways following FAK activation, and(3) to unravel possible extra-cellular cues that use FAK as an intracellular mediator during axonal development.I anticipate that some of the insights of this research will increase our understanding not just of the initial development of neural connections but also of normal plastic rearrangements of neural connections occurring in the adult nervous system.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSIDAD MIGUEL HERNANDEZ DE ELCHE · ELCHEКоординаторИспания
Връзки
Данни: CORDIS, © Европейски съюз