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Review
. 2015 Apr 8:9:116.
doi: 10.3389/fnins.2015.00116. eCollection 2015.

Neuronal polarization in the developing cerebral cortex

Akira Sakakibara  1 , Yumiko Hatanaka  2
Affiliations
Review

Neuronal polarization in the developing cerebral cortex

Akira Sakakibara et al. Front Neurosci. .

Abstract

Cortical neurons consist of excitatory projection neurons and inhibitory GABAergic interneurons, whose connections construct highly organized neuronal circuits that control higher order information processing. Recent progress in live imaging has allowed us to examine how these neurons differentiate during development in vivo or in in vivo-like conditions. These analyses have revealed how the initial steps of polarization, in which neurons establish an axon, occur. Interestingly, both excitatory and inhibitory cortical neurons establish neuronal polarity de novo by undergoing a multipolar stage reminiscent of the manner in which polarity formation occurs in hippocampal neurons in dissociated culture. In this review, we focus on polarity formation in cortical neurons and describe their typical morphology and dynamic behavior during the polarization period. We also discuss cellular and molecular mechanisms underlying polarization, with reference to polarity formation in dissociated hippocampal neurons in vitro.

Keywords: axon; cerebral cortex; excitatory cortical neuron; imaging; inhibitory cortical neuron; neuron; polarization.

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Figures

Figure 1
Figure 1
Sequential events of polarity formation as seen in hippocampal neurons in vitro and excitatory and inhibitory cortical neurons in vivo. Axon outgrowth processes are similar in vivo and in vitro, as axons emerge from non-polarized cells. (A) Schematic drawing showing neuronal polarity formation in dissociated hippocampal neurons in culture. (1) Immature neurons actively form filopodia and lamellipodia and then (2) extend multiple minor processes that randomly extend and retract their tips. (3) After several hours in culture, a minor process begins to grow rapidly and transform into an axon (symmetry break). (4) That axon further extends, and remaining processes differentiate into dendrites. (5) Finally, these differentiated processes mature. (B) Schematic drawing showing acquisition of neuronal polarity by excitatory cortical neurons. (I) Young neurons differentiated from ventricular zone (VZ) cells or through intermediate progenitors transform into multipolar cells, whose short processes repeatedly extend and retract in the subventricular zone (SVZ)/intermediate zone (IZ) over several hours. (II) A new process, which will become the axon (symmetry break), suddenly elongates tangentially. (III) The remaining processes, which will become dendrites, transform into a pia-directed leading process. (IV) Neurons gradually change shape, become bipolar, and migrate radially toward the pia, with the elongating axon as the trailing process. After reaching their final destination, axonal and dendritic processes mature. Most excitatory neurons differentiate into pyramidal cells (dendrites, green; axons, red). (C) Schematic drawing showing neuronal polarity formation by inhibitory neurons. These neurons are generated in the subpallium and migrate to the cortex. There they reach the marginal zone and execute multidirectional tangential migration, exhibiting a bipolar shape with a leading and trailing process. As development proceeds, they localize in the cortical plate, alternately extend and retract short processes, and exhibit low motility of somata. An axon then emerges (symmetry break) extending primarily toward the ventricle. Inhibitory neuron morphology is highly diverse: these subtypes include basket cells (the major inhibitory cortical neuron; dendrites, pink), Martinotti cells (the second major type; dendrites, yellow), double bouquet cells (the third major type; dendrites, blue) and others (Kubota, 2014). Whether dynamic process of axon formation depicted here correspond to all inhibitory neurons or subtypes of inhibitory neurons remains unknown.
Figure 2
Figure 2
Regulation of cortical neuron polarization. Axon formation in vivo is influenced by extracellular cues. Intracellular effectors regulating cytoskeletal dynamics and membrane vesicle transport function in the initiation, stabilization, and subsequent elongation of a single axon.
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