title: Spatial and temporal second messenger codes for growth cone turning.
abstract: Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1-dependent axon guidance. In filopodia, Netrin-1-dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California at San Diego, La Jolla, CA 92093, USA. xavier.nicol@inserm.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Nicol
authors.forename: Kwan Pyo
authors.initials: KP
authors.lastname: Hong
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D001369:Axons; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000502:physiology; D000075386:Netrin Receptors; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology; D011554:Pseudopodia; D011956:Receptors, Cell Surface / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology; D014981:Xenopus / Q000196:embryology*
chemical_list: D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D000242:Cyclic AMP; D002118:Calcium