Abstract
Background The function of the nervous system depends on precise and selective connections of neurons. Various guidance cues instruct axons in choosing their pathway, polarity of growth, termination of growth and also branching. In vitro studies demonstrated that signaling cascades activated by axonal guidance receptors could be modulated by cyclic nucleotides. Previous analyses of cGKI (cGMP dependent protein kinase I) deficient mice in our lab showed that cGMP signaling via cGKI is important in axonal pathfinding and connectivity of sensory neurons. Sensory axons bifurcate upon arrival at the dorsal root entry zone (DREZ) of the spinal cord. Embryonic cGKI knock-out mice lack the bifurcation of sensory axons at the DREZ, i.e. the ingrowing axon either turns rostrally or caudally. Here, we present results of the detailed analysis of axonal pathfinding errors in cGKI deficient mice and of the search for other components of cGMP signaling in dorsal root ganglions (DRG).
Highlights
The function of the nervous system depends on precise and selective connections of neurons
Screens for a role of guanylyl cyclases in sensory axon bifurcation carried out in our lab suggest that the natriuretic peptide receptor 2 (Npr2) might serve such a function in dorsal root ganglions (DRG) neurons
We studied embryos of mice lacking functional Npr2 using DiI labelling and observed axonal bifurcation errors identical to that in cGKI knock-out mice
Summary
The function of the nervous system depends on precise and selective connections of neurons. In vitro studies demonstrated that signaling cascades activated by axonal guidance receptors could be modulated by cyclic nucleotides. Previous analyses of cGKI (cGMP dependent protein kinase I) deficient mice in our lab showed that cGMP signaling via cGKI is important in axonal pathfinding and connectivity of sensory neurons. Sensory axons bifurcate upon arrival at the dorsal root entry zone (DREZ) of the spinal cord. Embryonic cGKI knock-out mice lack the bifurcation of sensory axons at the DREZ, i.e. the ingrowing axon either turns rostrally or caudally. We present results of the detailed analysis of axonal pathfinding errors in cGKI deficient mice and of the search for other components of cGMP signaling in dorsal root ganglions (DRG)
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