Although migrating, neocortical pyramidal neurons form a leading process and a trailing process, each becoming the axon or the dendrite ( Fig. 1B). In vivo, most neurons undergo axon–dendrite polarization during migration. On cell-cycle exit, mammalian neurons usually migrate over a long distance before reaching their final destination. Neuronal polarization can be divided into several specific steps in vivo. In vivo, pyramidal neurons acquire other key features of their terminal polarity, such as the axon initiation segment (AIS yellow cartridge) and dendritic spines (gray protrusions) during the first postnatal weeks of development. ( B) The axon–dendrite polarity of pyramidal neurons is derived from the polarized emergence of the trailing (TP) and leading processes (LP), respectively. Finally, stage 5 neurons are terminally differentiated pyramidal neurons harboring dendritic spines and the AIS. Stage 4 is characterized by rapid axon and dendritic outgrowth. Stage 3 represents a critical step when neuronal symmetry breaks and a single neurite grows rapidly to become the axon (purple), whereas other neurites acquire dendritic identity. At stage 1, immature postmitotic neurons display intense lamellipodial and filopodial protrusive activity, which leads to the emergence of multiple immature neurites, stage 2. ( A) In dissociated cultures, postmitotic cortical neurons display specific transitions as classically described for hippocampal neurons by Dotti and Banker (1988). Comparison of the sequence of events leading to the polarization of cortical pyramidal neurons in vivo and in vitro. Parallels between neuronal polarization in vitro and in vivo. 2005), provide a paradigm for (a) manipulating gene expression in progenitors (i.e., before neuronal polarization occurs on cell-cycle exit), and for (b) visualizing the earliest stages of neuronal polarization in a contextual cellular and molecular environment (i.e., in organotypic slices or intact embryonic brain) ( Hand et al. Recent advances in techniques such as in utero or ex utero cortical electroporation ( Saito and Nakatsuji 2001 Tabata and Nakajima 2001 Hatanaka and Murakami 2002 Hand et al. This can be critical for interpreting these experimental results. It is therefore important to keep in mind that, in this in vitro model, molecular manipulations act on previously polarized neurons that may retain some aspects of their initial polarization. It should be noted that in the classical E18 rat hippocampal cultures, most plated cells are polarized postmitotic neurons before dissociation. Careful analysis of these cultures led to the observation that cultured hippocampal neurons transition through several stages: from freshly plated stage-1 cells bearing immature neurites to stage-5 cells that show mature axons, dendrites, dendritic spines, and functional synapses ( Dotti et al. Historically, the advent of in vitro dissociated neuronal cultures provided an experimental template for improving our understanding of the cell biology of neuronal polarity, including the specification of the molecular identity of axon and dendrites ( Goslin and Banker 1989 Craig and Banker 1994). In this article, we focus our attention on the extracellular cues and signaling pathways required in vivo for axon initiation and axon extension. However, the importance of extracellular cues to axon initiation and outgrowth in vivo is emerging as a major theme in neural development (īarnes and Polleux 2009). In vitro, axon initiation and elongation are largely intrinsic properties of neurons that are established in the absence of relevant extracellular cues. At present, only a few of the genes identified using in vitro approaches have been shown to be required for axon initiation and outgrowth in vivo. This approach became, and remains, the dominant model to study axon initiation and growth and has yielded the identification of many molecules that regulate axon formation in vitro (ĭotti et al. Remarkably, neurons can polarize to form a single axon, multiple dendrites, and later establish functional synaptic contacts in reductionist in vitro conditions. This article reviews what is known about the cellular and molecular mechanisms underlying the ability of neurons to initiate and extend a single axon during development. Action potentials then propagate along the axon, which makes presynaptic contacts onto target cells. Dendrites integrate synaptic inputs, triggering the generation of action potentials at the level of the soma. Dendrites and axons are molecularly and functionally distinct domains. The ability of neurons to form a single axon and multiple dendrites underlies the directional flow of information transfer in the central nervous system.
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