Can regeneration be enhanced by modulating the intrinsic receptor signaling of injured axons? We believe that studies on protease-mediated axon guidance molecule processing will provide important clues for these questions, and that the manipulation of individual proteases with high substrate-specificity might serve as Selleck Hydroxychloroquine clinically relevant targets to enhance regeneration. We would like to thank Dr. Jerry Sliver and Dr. Veronica Shubayev for critical reading of the manuscript and Jamie Simon for assistance with illustrations. We are also grateful to Dario Bonanomi, Onanong Chivatakarn,

and other members of the Pfaff lab for advice and discussions. G.B. is supported by the Howard Hughes Medical Institute and Pioneer foundation, and S.L.P. is a Howard Hughes Medical Institute Investigator. Research on axon guidance in the lab is supported by NINDS grants NS054172 and NS037116. “
“To integrate into neuronal circuits, newly generated neurons engage in a series of

stereotypical developmental events. After exit from the cell-cycle, postmitotic neurons first undergo axo-dendritic polarization, a process that encompasses the initial specification of axons and dendrites selleck chemical and their coordinate growth giving rise to the unique neuronal shape. Concurrently, many neurons undergo extensive migration to reach their final destinations in the brain. Axons grow to their appropriate targets, dendrites arborize and prune to cover the demands of their receptive field, and synapses form and are refined to ensure proper connectivity. How neurons accomplish all these tasks has been the subject of intense scrutiny during the past few decades. A large body of work has established that these fundamental developmental events are regulated by extrinsic cues including

secreted polypeptide growth factors, adhesion molecules, extracellular matrix components, and neuronal activity (Dijkhuizen and Dichloromethane dehalogenase Ghosh, 2005b, Huber et al., 2003, Katz and Shatz, 1996, Markus et al., 2002a, McAllister, 2002 and Tessier-Lavigne and Goodman, 1996). Extrinsic cues are thought to regulate both the overall design of neuronal shape as well as their fine structural elements such as axon branch points and dendritic spines. Growth factors, guidance proteins, and other extrinsic cues act via specific cell surface receptor proteins, which in turn regulate intracellular signaling proteins that directly influence cytoskeletal elements. Members of the Rho GTPase family of proteins and protein kinases have emerged as key signaling intermediaries that couple the effects of extrinsic cues to the control of actin and microtubule dynamics (Dhavan and Tsai, 2001, Dickson, 2002, Govek et al., 2005, Hur and Zhou, 2010, Luo, 2000, O’Donnell et al., 2009 and Wayman et al., 2008b).