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

First Author  Ter-Avetisyan G Year  2014
Journal  J Neurosci Volume  34
Issue  3 Pages  737-47
PubMed ID  24431432 Mgi Jnum  J:205571
Mgi Id  MGI:5545834 Doi  10.1523/JNEUROSCI.4183-13.2014
Citation  Ter-Avetisyan G, et al. (2014) Bifurcation of Axons from Cranial Sensory Neurons Is Disabled in the Absence of Npr2-Induced cGMP Signaling. J Neurosci 34(3):737-47
abstractText  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 Ialpha (cGKIalpha) 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 cGKIalpha 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.
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