title: Bifurcation of axons from cranial sensory neurons is disabled in the absence of Npr2-induced cGMP signaling.
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 Iα (cGKIα) 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 cGKIα 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.
authors.affiliation: Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Gohar
authors.initials: G
authors.lastname: Ter-Avetisyan
authors.forename: Fritz G
authors.initials: FG
authors.lastname: Rathjen
authors.forename: Hannes
authors.initials: H
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001369:Axons / Q000737:chemistry* / Q000502:physiology; D003391:Cranial Nerves / Q000737:chemistry* / Q000473:pathology / Q000502:physiology; D006152:Cyclic GMP / Q000235:genetics* / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D017461:Receptors, Atrial Natriuretic Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D011984:Sensory Receptor Cells / Q000737:chemistry* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics*; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D006152:Cyclic GMP; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B
keywords: CNP; Npr2; axonal branching; cGKI; cGMP signaling; cranial sensory ganglia