Nature Neuroscience 9, 195 - 204 (2006)
Published online: 15 January 2006; | doi:10.1038/nn1627
Serum response factor controls neuronal circuit assembly in the hippocampusBernd Knöll1, Oliver Kretz2, Christine Fiedler1, Siegfried Alberti1, Günther Schütz3, Michael Frotscher2
& Alfred Nordheim11
Interfakultäres Institut für Zellbiologie, Abt. Molekularbiologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany. 2
Institut für Anatomie und Zellbiologie, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany. 3
Deutsches Krebsforschungszentrum (DKFZ), Molekularbiologie der Zelle I, Heidelberg, Germany.
Correspondence should be addressed to Alfred Nordheim alfred.nordheim@uni-tuebingen.de Higher organisms rely on multiple modes of memory storage using the hippocampal network, which is built by precisely orchestrated mechanisms of axonal outgrowth, guidance and synaptic targeting. We demonstrate essential roles of the transcription factor serum response factor (SRF), a sensor of cytoskeletal actin dynamics, in all these processes. Conditional deletion of the mouse Srf gene reduced neurite outgrowth and abolished mossy fiber segregation, resulting in ectopic fiber growth inside the pyramidal layer. SRF-deficient mossy fibers aberrantly targeted CA3 somata for synapse formation. Axon guidance assays showed that SRF was a key mediator of ephrin-A and semaphorin guidance cues; in SRF-deficient neurons, these resulted in the formation of F-actin–microtubule rings rather than complete growth cone collapse. Dominant-negative variants of the SRF cofactor megakaryocytic acute leukemia (MAL) severely impeded neurite outgrowth and guidance. These data highlight essential links between SRF-mediated transcription and axon guidance and circuit formation in the hippocampus.
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