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Bifurcation of axons from cranial sensory neurons is disabled in the absence of Npr2-induced cGMP signaling

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Item Type:Article
Title:Bifurcation of axons from cranial sensory neurons is disabled in the absence of Npr2-induced cGMP signaling
Creators Name:Ter-Avetisyan, G. and Rathjen, F.G. and Schmidt, H.
Abstract:Axonal branching is a prerequisite for the establishment of complex neuronal circuits and their capacity for parallel information processing. Previously, we have identified a cGMP signaling pathway composed of the ligand C-type natriuretic peptide (CNP), its receptor, the guanylyl cyclase natriuretic peptide receptor 2 (Npr2), and the cGMP-dependent kinase I{alpha} (cGKI{alpha}) that regulates axon bifurcation of dorsal root ganglion (DRG) neurons in the spinal cord. Now we asked whether this cascade also controls axon bifurcation elsewhere in the nervous system. An Npr2-lacZ reporter mouse line was generated to clarify the pattern of the CNP receptor expression. It was found that during the period of axonal outgrowth, Npr2 and cGKI{alpha} were strongly labeled in neurons of all cranial sensory ganglia (gV, gVII, gVIII, gIX, and gX). In addition, strong complementary expression of CNP was detected in the hindbrain at the entry zones of sensory afferents. To analyze axon branching in individual Npr2-positive neurons, we generated a mouse mutant expressing a tamoxifen-inducible variant of Cre recombinase expressed under control of the Npr2-promoter (Npr2-CreER(T2)). After crossing this strain with conditional reporter mouse lines, we revealed that the complete absence of Npr2 activity indeed prohibited the bifurcation of cranial sensory axons in their entrance region. Consequently, axons only turned in either an ascending or descending direction, while collateral formation and growth of the peripheral arm was not affected. These findings indicate that in neurons of the cranial sensory ganglia, as in DRG neurons, cGMP signals are necessary for the execution of an axonal bifurcation program.
Keywords:Axonal Branching, cGKI, cGMP Signaling, CNP, Cranial Sensory Ganglia, Npr2, Animals, Mice
Source:Journal of Neuroscience
ISSN:0270-6474
Publisher:Society for Neuroscience
Volume:34
Number:3
Page Range:737-747
Date:15 January 2014
Official Publication:https://doi.org/10.1523/JNEUROSCI.4183-13.2014
PubMed:View item in PubMed

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