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The Journal of Neuroscience, April 9, 2008, 28(15):3920-3924; doi:10.1523/JNEUROSCI.0547-08.2008

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Brief Communications
Soluble Adenylyl Cyclase Is Not Required for Axon Guidance to Netrin-1

Simon W. Moore,¹ Karen Lai Wing Sun,¹ Fang Xie,² Philip A. Barker,¹ Marco Conti,² and Timothy E. Kennedy¹

¹Centre for Neuronal Survival, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4, and ²Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317

Correspondence should be addressed to Timothy E. Kennedy at the above address. Email: timothy.kennedy{at}mcgill.ca

During development, axons are directed to their targets by extracellular guidance cues. The axonal response to the guidance cue netrin-1 is profoundly influenced by the concentration of cAMP within the growth cone. In some cases, cAMP affects the sensitivity of the growth cone to netrin-1, whereas in others it changes the response to netrin-1 from attraction to repulsion. The effects of cAMP on netrin-1 action are well accepted, but the critical issue of whether cAMP production is activated by a netrin-1 induced signaling cascade remains uncertain. A previous report has suggested that axon guidance in response to netrin-1 requires cAMP production mediated by soluble adenyl cyclase (sAC). We have used genetic, molecular and biochemical strategies to assess this issue. Surprisingly, we found only extremely weak expression of sAC in embryonic neurons and determined that, under conditions where netrin-1 directs axonal pathfinding, exposure to netrin-1 does not alter cAMP levels. Furthermore, although netrin-1-deficient mice exhibit major axon guidance defects, we show that pathfinding is normal in sAC-null mice. Therefore, although cAMP can alter the response of axons to netrin-1, we conclude that netrin-1 does not alter cAMP levels in axons attracted by this cue, and that sAC is not required for axon attraction to netrin-1.

Key words: spinal commissural neurons; dorsal root ganglion; DRG; nerve growth factor; NGF; protein kinase A; PKA; pituitary adenylate cyclase-activating polypeptide; PACAP

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Received Sept. 18, 2007; accepted Feb. 27, 2008.

Correspondence should be addressed to Timothy E. Kennedy at the above address. Email: timothy.kennedy{at}mcgill.ca

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