@article {138,
	title = {Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {110},
	year = {2013},
	month = {2013 Jan 22},
	pages = {1524-9},
	abstract = {<p>The role of electrical activity in axon guidance has been extensively studied in vitro. To better understand its role in the intact nervous system, we imaged intracellular Ca(2+) in zebrafish primary motor neurons (PMN) during axon pathfinding in vivo. We found that PMN generate specific patterns of Ca(2+) spikes at different developmental stages. Spikes arose in the distal axon of PMN and were propagated to the cell body. Suppression of Ca(2+) spiking activity in single PMN led to stereotyped errors, but silencing all electrical activity had no effect on axon guidance, indicating that an activity-based competition rule regulates this process. This competition was not mediated by synaptic transmission. Combination of PlexinA3 knockdown with suppression of Ca(2+) activity in single PMN produced a synergistic increase in the incidence of pathfinding errors. However, expression of PlexinA3 transcripts was not regulated by activity. Our results provide an in vivo demonstration of the intersection of spontaneous electrical activity with the PlexinA3 guidance molecule receptor in regulation of axon pathfinding.</p>
},
	keywords = {Animals, Animals, Genetically Modified, Axons, Calcium Signaling, Gene Knockdown Techniques, Humans, Motor Neurons, Neural Pathways, Potassium Channels, Inwardly Rectifying, Receptors, Cell Surface, Recombinant Proteins, Synaptic Transmission, Zebrafish, Zebrafish Proteins},
	issn = {1091-6490},
	doi = {10.1073/pnas.1213048110},
	author = {Plazas, Paola V and Nicol, Xavier and Spitzer, Nicholas C}
}
@article {137,
	title = {Spatial and temporal second messenger codes for growth cone turning.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {108},
	year = {2011},
	month = {2011 Aug 16},
	pages = {13776-81},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Axons, Calcium, Cells, Cultured, Cyclic AMP, Growth Cones, Nerve Growth Factors, Neurons, Pseudopodia, Receptors, Cell Surface, Second Messenger Systems, Tumor Suppressor Proteins, Xenopus},
	issn = {1091-6490},
	doi = {10.1073/pnas.1100247108},
	author = {Nicol, Xavier and Hong, Kwan Pyo and Spitzer, Nicholas C}
}
