Abstract
The axon initial segment (AIS) is responsible for both the modulation of action potentials and the maintenance of neuronal polarity. Yet, the molecular mechanisms controlling its assembly are incompletely understood. Our study in single electroporated motor neurons in mouse embryos revealed that AnkyrinG (AnkG), the AIS master organizer, is undetectable in bipolar migrating motor neurons, but is already expressed at the beginning of axonogenesis at E9.5 and initially distributed homogeneously along the entire growing axon. Then, from E11.5, a stage when AnkG is already apposed to the membrane, as observed by electron microscopy, the protein progressively becomes restricted to the proximal axon. Analysis on the global motor neurons population indicated that Neurofascin follows an identical spatio-temporal distribution, whereas sodium channels and β4-spectrin only appear along AnkG+ segments at E11.5. Early patch-clamp recordings of individual motor neurons indicated that at E12.5 these nascent AISs are already able to generate spikes. Using knock-out mice, we demonstrated that neither β4-spectrin nor Neurofascin control the distal-to-proximal restriction of AnkG.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-013-0578-7) contains supplementary material, which is available to authorized users.
Highlights
The axon initial segment (AIS) constitutes a microdomain in neurons that has emerged as a key structural and functional entity in the last few years
Analysis on the global motor neurons population indicated that Neurofascin follows an identical spatio-temporal distribution, whereas sodium channels and b4-spectrin only appear along AnkG? segments at E11.5
Spinal motor neurons (MNs) are favorable neurons for undertaking in vivo analysis of AIS assembly because their axons can be observed along their complete length in embryonic spinal cord sections
Summary
The axon initial segment (AIS) constitutes a microdomain in neurons that has emerged as a key structural and functional entity in the last few years. The AIS contributes to the maintenance of neuronal polarity (Hedstrom et al 2008; Sobotzik et al 2009; Rasband 2010): it constitutes a diffusion barrier limiting the mobility of both membrane (Winckler et al 1999; Nakada et al 2003) and cytoplasmic molecules (Song et al 2009). AnkyrinG (AnkG) (Kordeli et al 1995), considered as the central AIS organizer, interacts with both the actin cytoskeleton via b4-spectrin (Berghs et al 2000; Komada and Soriano 2002), and microtubules through the EB3 protein (Leterrier et al 2011b).
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