Pruning of unspecific neurites is an important mechanism during neuronal morphogenesis. sensory neurons prune their dendrites during metamorphosis. Pruning dendrites are severed in their proximal regions. Prior to severing, dendritic microtubules undergo local disassembly, and dendrites thin extensively through local endocytosis. Microtubule disassembly requires a katanin homologue, but the signals initiating microtubule breakdown are not known. Here, we show that the kinase PAR-1 is required for pruning and dendritic microtubule breakdown. Our data show that neurons lacking PAR-1 fail to break down dendritic microtubules, and PAR-1 is required for an increase in neuronal microtubule dynamics at the onset of metamorphosis. Mammalian PAR-1 is a known Tau kinase, and genetic interactions suggest that PAR-1 promotes microtubule breakdown largely via inhibition of Tau also in Finally, PAR-1 is also required for dendritic thinning, suggesting that microtubule breakdown might precede ensuing plasma membrane alterations. Our results shed light on the signaling cascades and epistatic relationships involved in neurite destabilization during dendrite pruning.

Zusammenfassung:Die Entwicklung des Nervensystems beinhaltet sowohl progressive Phasen, in denen Neuriten und Synapsen geformt werden, als auch regressive Phasen, in denen überzählige Fortsätze zurückgezogen und abgebaut werden. Solche regressiven Mechanismen werden auch als

Abstract:The axons, dendrites and synapses of neurons are among the most intricate structures cells can build. Their morphogenesis involves growth mechanisms, but also regressive mechanisms like retraction or degeneration of supernumerary or non-specific processes. Regressive mechanisms are collectively known as pruning. Pruning can serve the specification of neuronal circuits or the removal of developmentally intermediate structures. Pruning can affect both single synapses or long stretches of neurite. Here, we introduce well-characterized models of developmental pruning in mammals and