Perhaps the interface offers an opportunity to learn about the logic of two behaviorally related

systems for the price of one interrogation. We thank Jay Bikoff, Andrew Fink, Samaher Fageiry, and Mark Churchland for discussions that helped shape the opinions in this essay. T.M.J. thanks Liz Wright and Rob Brownstone for providing a dose of Halifax serenity needed for the completion of this essay. This work was supported by NINDS and ProjectALS. T.M.J. is an HHMI investigator; both A.M. and E.A. are Howard Hughes Medical Institute Fellows of The Helen Hay Whitney Foundation. “
“Although psychological experts tell us to avoid becoming too compartmentalized in our thinking, compartmentalization is a key feature of neurons. Generation of an axonal and LBH589 in vivo a somatodendritic domain is a prerequisite for the directed flow of information in the nervous system. Therefore, the establishment of the complex neuronal morphology with one axon and several dendrites is a critical step during neuronal differentiation. The underlying mechanisms that regulate the formation of neuronal

polarity are currently under intense investigation. In culture, hippocampal neurons start off as round, unpolarized cells that transform into a multipolar cell with several short neurites that all have the potential Ibrutinib molecular weight to become an axon. Only one of these neurites will grow quickly and turn into an axon while the other neurites only start to grow later and become dendrites. Stable microtubules in the axon shaft and a dynamic actin network in the axon growth cone are instructive for axon growth (Stiess and Bradke, 2010). However, so far, it has remained Ribonucleotide reductase unclear how a neuron coordinates intracellular changes that could lead to the growth of the

axon and the simultaneous halt of the other neurites. The reported restriction of growth permissive proteins, including the partitioning-defective (Par) proteins Par3 and Par6 (Shi et al., 2003) and Rap1B (Schwamborn et al., 2007), to the nascent axon may present a hallmark of neuronal polarity. The asymmetric localization of axon determinants can be achieved by transport into one process (Bradke and Dotti, 1997), e.g., along selectively stabilized microtubules in the growing axon (Stiess and Bradke, 2010). In addition, the selective stabilization of the proteins in the future axon might lead to the asymmetric localization of polarizing proteins. Indeed, the small GTPase Rap1B in its inactive form becomes ubiquitinated and thus targeted for proteasomal degradation by the E3 Ligase Smurf2 in the minor neurites (Schwamborn et al., 2007). The resulting axonal localization specifies the future axon and is required for neuronal polarization. In this issue of Neuron, Cheng et al.