Research Report 2010 - MDC

PhD studentsJadwiga CholewaRogerio CraveiroVincent Ramillon*Agne StonkuteGohar Ter-Avetisyan*Philip Tröster*Master of Science studentsMie Kristensen*Katharina Seifferth*Steven Sievers*Daniela Spohr*Technical assistantsHannelore DrechslerMadlen DriesnerMechthild HenningSecretariatBirgit Cloos (part time)*part of the period reportedFigure 1. A cGMP signaling cascade important for axonalbifurcation.Our starting point was the cGKI (encircled) which we showed to beimportant for branching. During the past funding period we usedgenetic ablation techniques to characterize the receptor guanylylcyclase Npr2 and its ligand CNP (natriuretic peptide C) and showedthat these components are essential for bifurcation. Furthermore,several phosphorylation targets have been identified by biochemicalapproaches; however, it is currently unknown whether they are alsoimportant for bifurcation.Figure 2. Impairment of bifurcation in the absence of cGMP signaling.A shows a single bifurcating sensory axon in a normal mouse embryo while B reveals an axon in the absence of CNP signaling which turnsbut does form T-shaped branches.The transmembrane protein CALEB is implicatedin synapse maturationBy a detailed biochemical and histological characterizationwe revealed that CALEB is primarily localized in thesomato-dendritic compartment of a neuron and partiallyco-localizes with synapses (Figure 3). It is stronglyexpressed in early postnatal stages of the mouse whenthe majority of synapses and dendritic trees areformed.Dendrites are the input regions of a neuron. In manycases they arborize into a tree like structure by anextensive and complex branching program. Earlystages of dendrite development might be regulated byintrinsic programs specific for a neuron type whichmight then be modulated by different external signalsdetected by specific receptor proteins. During thedevelopment of dendritic trees CALEB appears to berequired for specific aspects of synapse maturation. Forexample, CALEB-deficient synapses displayed higherFunction and Dysfunction of the Nervous System 159