What Makes Axons Branch in the Brain Forest?
Previous studies by the scientists from Professor Rathjen’s group had revealed that a signalling pathway that uses a specific messenger, the second messenger cGMP, controls the bifurcation (a special mode of branching) of axons from dorsal root ganglia (DRG) neurons at the entry zones of the spinal cord. The scientists were able to show that this signalling cascade is started by the secreted factor CNP (short for C-type natriuretic peptide), which activates a receptor on the surface of the axon, Npr2 (guanylyl cyclase). Npr2 produces cGMP and subsequently a cGMP-dependent protein kinase (cGKIalpha) that turns on and switches off various target proteins. In the absence of any one of these components, DRG axons no longer bifurcate, but instead change their direction – either rostrally (upwards) or caudally (downwards).
Following up on these results, a new study by Dr. Gohar Ter-Avetisyan, Professor Rathjen and Dr. Hannes Schmidt demonstrated that axons of neurons from cranial sensory ganglia – which amongst other things process information from the mice’s whisker hairs or the auditory and vestibular systems – also use this signalling cascade to branch when they enter the hindbrain. The MDC researchers generated transgenic mice in order to follow the path of individual axons within the dense forest of neuronal circuits. They were able to show that the absence of cGMP signalling causes a complete loss of bifurcation of all cranial sensory axons.
In summary, these investigations demonstrate that both dorsal root and cranial sensory ganglia neurons depend on CNP-induced cGMP signalling to branch upon reaching the central nervous system. Future studies with mice that allow the selective inactivation of cGMP signalling components only in sensory neurons should help to resolve the impact of impaired axon bifurcation on sensory information processing.
Gohar Ter-Avetisyan, Fritz G. Rathjen, and Hannes Schmidt
Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
Molecular imaging of single axon path of cranial sensory neurons from wild-type (left panel) and Npr2 knockout mice (centre panel) shows the complete lack of sensory axon bifurcation at the embryonic hindbrain in the absence of Npr2 as summarised in the schematic diagram (right panel). (Graphic and copyright: Gohar Ter-Avetisyan, Fritz Rathjen, Hannes Schmidt)
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