APC ain't always necessary for axons

Abstract

Like many neuroscientists, Rusan et al. considered that the mechanism controlling axonal positioning and outgrowth might be the same in all neurons. As they now show, however, one neuron's must-have axon-promoting protein is virtually dispensable in other neurons. Figure 1 A central brain neuron grows a perfectly good axon even in the absence of APC. In a young neuron, multiple mini neurites protrude until one is chosen to become the axon. A microtubule-associated protein called APC was thought to be required for axon outgrowth, as dominant-negative APC expression in cultured neurons reduced axon growth dramatically. Other reports had suggested that APC delivers a polarity protein called Par3, necessary for axon growth, to the chosen neurite. Despite the strong evidence for APC's axon-promoting role, definitive knockout experiments in neurons were limited to one study, which showed that medulla neurons behaved much as expected—no APC, no axon extension. Now, the same lab have found that neurons from the central brain, mushroom body, and lobular plug will happily grow axons without APC. Cells from these parts of the brain were not entirely normal: precursor neuroblasts had slightly longer cell cycles and some had bent spindles. Though, neither problem prevented mitosis. The need for APC in some neurons but not others seems to reflect a requirement for Wnt signaling. As well as its cytoskeletal role, APC is a downstream regulator of Wnt, and while medulla neurons need Wnt for axon growth, the other types of neurons did not. It will be of interest to check whether hippocampal neurons, where the dominant-negative experiments were carried out, are also Wnt responsive. Rusan, N.M., et al. 2008. J. Cell Biol. .10.1083/jcb.200807079 [PubMed] [Cross Ref]