STKE: Dissecting Growth Cone Guidance

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Science  11 Apr 2003:
Vol. 300, Issue 5617, pp. 217c
DOI: 10.1126/science.300.5617.217c

The growth cones of developing neurons take twists and turns as they strive to reach their targets. Their paths are marked by attractive and repulsive cues (chemotropic ligands) that they encounter along the way. These ligands activate receptors on the surface of the growth cone. Campbell and Holt report that in cultured Xenopus retinal growth cones, three different chemotropic ligands—netrin-1, semaphorin3A (Sema3A), and lysophosphatidic acid (LPA)—stimulate distinct, but overlapping, signaling pathways. Netrin-1 and Sema3A activated the p42 and p44 mitogen-activated protein kinases (MAPKs). The p38 MAPK, normally associated with stress responses, was activated in cells treated with netrin-1 or LPA. Studies with antibodies to the active, cleaved form of caspase-3 revealed that caspase-3 was activated in response to LPA or netrin-1. The authors discuss the potential role of caspase-3—better known as a component of pathways leading to apoptosis or cell death—in axon guidance and note similarities between the chemotropic pathways implicated in this work with those thought to regulate synaptic plasticity.—LBR

Neuron 37, 939 (2003).

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