Clearly, this model and the precise functions of AC in growth cone actin dynamics and guidance responses require further studies, which may benefit from the emerging super resolution imaging techniques (Toomre and Bewersdorf, 2010). Microtubules (MTs), the cylindrical filaments each consisting of 13 protofilaments, are a major cytoskeletal system within the axonal and dendritic projections. MTs are intrinsically polarized due to their head-to-tail assembly from α/β tubulin heterodimers. While the plus and minus ends of MTs favor polymerization and depolymerization, Imatinib clinical trial respectively, the minus ends of MTs are often capped and stabilized inside cells

(Dammermann et al., 2003). Instead, MT plus ends exhibit “dynamic instability,” in which

their polymerization-based growth is interrupted by “catastrophe” phases of rapid depolymerization and shrinkage (Cassimeris et al., 1987). It is believed that dynamic instability provides MTs with the ability to quickly remodel their organization and selectively grow in response to extracellular signals. Selleckchem GSK2118436 In neurons, most of MTs are believed to be polymerized from the centrosome, but are severed, released, and transported into long axons and dendritic arbors where they form dense arrays (or bundles). These condensed MT arrangements are the structural foundation for the extension and maintenance of highly elongated and elaborated nerve processes. In addition, MT arrays serve as the railway tracks for long-range transport of cellular organelles and cargos, which is essential for the survival and function of the neuron (Hirokawa et al., 2010). Thymidine kinase Finally, spatiotemporally regulated dynamics of these MTs may play an important role in specifying axonal and dendritic polarization (Witte et al., 2008). How MTs are involved in the directional responses

of the growth cone has only begun to be elucidated (Dent et al., 2011, Gordon-Weeks, 2004 and Lowery and Van Vactor, 2009). The dense MT arrays in the neurite shaft typically terminate in the growth cone C region, with a small number of MTs splaying out into the actin rich P region (Figure 2). These individual MTs appear to exhibit a high degree of dynamics and track along the actin filaments (Schaefer et al., 2002). It should be noted that MTs in axons are organized in uniform polarity such that individual MTs in the growth cone are pioneered by their plus ends. Therefore, the behavior of MTs exploring the growth cone P region is largely dictated by how their dynamic instability is regulated. It is believed that actin-based growth cone movement requires the local stabilization of dynamic MTs exploring the P region, followed by site-directed MT polymerization and delivery of cellular cargos to consolidate the space created by the forward movement of the growth cone.