Research Report 2010 - MDC

Structure of the GroupGroup LeaderFritz G. RathjenScientistsRené JüttnerChristopher PatzkeHannes SchmidtLuminita Stoenica*Fritz G. RathjenNeuronal ConnectivityThe functioning of the nervous system is critically dependent on the correct wiring ofneurons which is primarily established during embryonic and early postnataldevelopment. To generate precise circuits neuron extends an axon and dendrites which areguided to their targets by growth cones. This highly motile structure at the tip of axons ordendrites is steered by molecular guidance cues located in the local environment. In thetarget area neurons then establish synapses that are the fabric of communication betweenneurons. Our research group focuses currently on the following molecular aspects on theformation of neuronal connectivity: branching of axons and dendrites and formation andmaturation of synapses.Axonal and dendritic branching are key steps inregulating neuronal connectivityOne important prerequisite to generate the complexcircuits of the mature nervous system is the arborizationof axons and dendrites. This key process enables anindividual neuron to innervate multiple targets wherebyinformation from neurons in various locations canbe integrated. Branching is therefore a critical step inthe formation of complex neuronal circuits. Despite itsimportance the extracellular signals and the intracellularsignaling machinery that regulate branching haveremained poorly understood. To investigate theseprocesses we concentrated on sensory axons projectinginto the spinal cord and on cortical neurons.A cGMP signaling cascade is essential for branchingof sensory axonsSensory axons enter the spinal cord at the dorsal rootentry zone where they branch into a rostral and a caudalarm. These two arms remain confined to lateralregions of the cord and grow over several segments inboth directions. Collaterals are then generated by buddingfrom these stem axons which extend into the graymatter of the cord. Sensory axons therefore reveal atleast two branching modes: splitting of the growthcone when arriving at the cord followed by budding ofcollaterals (interstitial branching) from the stem axons.By genetic ablation and by single axon tracing werevealed that a cGMP-dependent signaling cascade isimportant for sensory axon branching at the dorsal rootentry zone. In the absence of either the natriuretic peptideC (CNP), the receptor guanylyl cyclase Npr2 or thecGMP-dependent kinase I (cGKI) axons are unable toform a T-shaped branch when entering the spinal cord(Figure 1 and Figure 2). Instead axons turn in rostral orcaudal directions. The other branching mode – the formationof collaterals – is not regulated by this signalingcascade.Our current efforts concentrate on the identification offurther upstream and downstream components toestablish a complete picture of this signaling cascadeas well as on other axon systems that regulate branchingby this signaling cascade.158 Function and Dysfunction of the Nervous System