title: Regulation by protein kinase A switching of axonal pathfinding of zebrafish olfactory sensory neurons through the olfactory placode-olfactory bulb boundary.
abstract: Cumulative evidence suggests that neural network formation requires an ingenious regulation of the attractive and repulsive responses of growing axons to guidance cues. We examined the role of intracellular protein kinase A (PKA) signaling in the axonal pathfinding of olfactory sensory neurons in transparent zebrafish embryos. Microinjection of an olfactory marker protein gene promoter-driven double-cassette vector directed the expression of both the dominant form of PKA and green fluorescent protein fused with the microtubule-associated protein tau in the same olfactory neurons. The dominant-negative form of PKA enhanced the turning of olfactory neuron axons in the olfactory placode, whereas the disturbance effect of the constitutively active form on the axonal pathfinding was prominent in the olfactory bulb. Consistently, forskolin treatment severely inhibited the axonal extension in the olfactory bulb, but not in the olfactory placode. These results suggest that the switching of PKA signaling in developing olfactory sensory neurons is important for axonal pathfinding through the boundary between the olfactory placode and the olfactory bulb in vivo. We thus propose that the regulation of PKA signaling plays a key role in the long-distance axonal pathfinding through intermediate guideposts.
authors.affiliation: Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, and SORST, Japan Science and Technology Corporation, Tokyo 113-0033, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Aya
authors.initials: A
authors.lastname: Ito
authors.forename: Naoto
authors.initials: N
authors.lastname: Matsuda
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D006801:Humans; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology*; D051842:Olfactory Marker Protein; D018034:Olfactory Receptor Neurons / Q000196:embryology* / Q000201:enzymology / Q000502:physiology*; D016415:Sequence Alignment; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D009419:Nerve Tissue Proteins; C497597:OMP protein, human; D051842:Olfactory Marker Protein; D029961:Zebrafish Proteins; C497600:ompb protein, zebrafish; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases