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Cell signalling cascades regulating neuronal growth-promoting and inhibitory cues
S D Skaper1, S E Moore, F S Walsh
1Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK.
Progress in Neurobiology
|December 1, 2001
Summary
Neuronal growth cones use guidance cues to navigate the nervous system. Cell adhesion molecules and growth inhibitory proteins mediate this process, impacting synaptic plasticity and learning.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Axon guidance is crucial for nervous system development, ensuring neurons reach correct targets.
- Axonal growth cones interpret guidance cues that promote or repel their advance.
- Cell adhesion molecules (CAMs) and inhibitory proteins direct neurite outgrowth.
Purpose of the Study:
- To review major themes in axon guidance and neurite outgrowth.
- To highlight the roles of cell adhesion molecules and inhibitory signals.
- To discuss signal transduction pathways involved in neuronal navigation.
Main Methods:
- In vitro assays demonstrating CAM functions.
- Review of existing literature on guidance cues and signaling pathways.
- Analysis of roles in synaptic plasticity, learning, and memory.
Main Results:
- CAMs like N-CAM, N-cadherin, and L1 glycoprotein promote axonal growth over various cells.
- Fibroblast growth factor receptor tyrosine kinase is implicated in the CAM pathway.
- Negative signals including Nogo, myelin-associated glycoprotein, and Semaphorins inhibit neurite growth.
- Rho kinase-mediated signaling is emerging in neurite outgrowth inhibition.
Conclusions:
- Axon guidance relies on a complex interplay of attractive and repulsive cues.
- CAMs are vital for neuronal pathfinding and synaptic plasticity.
- Understanding these mechanisms is key to advancing neuroscience research.