C-type natriuretic peptide (CNP) is a bifurcation factor for sensory neurons

Neuronal circuits are shaped during development by the coordinated action of guidance factors and signals that regulate axonal branching. Unlike guidance cues, the molecules and signaling cascades that underlie axonal branching remain to be resolved. Here we show that the secreted molecule C-type na...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-09, Vol.106 (39), p.16847-16852
Main Authors: Schmidt, Hannes, Stonkute, Agne, Jüttner, René, Koesling, Doris, Friebe, Andreas, Rathjen, Fritz G
Format: Article
Language:English
Subjects:
Animals
Axons
Biological Sciences
Brain
Branching
Cognition & reasoning
Cyclic GMP - metabolism
Embryos
Growth cones
Mice
Mice, Transgenic
Molecules
Mutation
Natriuretic Peptide, C-Type - genetics
Natriuretic Peptide, C-Type - metabolism
Natriuretic peptides
Neurons
Neuroscience
Nitric oxide
Patch-Clamp Techniques
Peptides
Physiological regulation
Receptors
Receptors, Atrial Natriuretic Factor - genetics
Receptors, Atrial Natriuretic Factor - metabolism
Rodents
Sensory Receptor Cells - metabolism
Signal Transduction
Spinal cord
Spinal Cord - metabolism
Spinal Nerve Roots - metabolism
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Summary:Neuronal circuits are shaped during development by the coordinated action of guidance factors and signals that regulate axonal branching. Unlike guidance cues, the molecules and signaling cascades that underlie axonal branching remain to be resolved. Here we show that the secreted molecule C-type natriuretic peptide (CNP) induces a cGMP signaling cascade via its receptor particulate guanylyl cyclase Npr2 which is essential for sensory axon bifurcation at the dorsal root entry zone (DREZ) of the spinal cord. In contrast, another form of sensory axon branching--collateral formation--is not affected by this pathway. We also demonstrate that cGMP signaling via the nitric oxide-stimulated soluble guanylyl cyclase system (NO-GC) is dispensable for sensory axon branching. Functionally, the bifurcation error in CNP mutant mice is maintained at mature stages and results in a reduced input on secondary neurons as detected by patch-clamp recordings.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0906571106