Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex

Namba, Tsuneo; Kibe, Yuji; Funahashi, Yasuhiro; Nakamuta, Shinichi; Takano, Tetsuya; Ueno, Taiji; Shimada, Akiko; Kozawa, Sachi; Okamoto, Masakazu; Shimoda, Yasushi; Oda, Kanako; Wada, Yoshino; Masuda, Tomoyuki; Sakakibara, Akira; Igarashi, Michihiro; Miyata, Takaki; Faivre‐Sarrailh, Catherine; Takeuchi, Kosei; Kaibuchi, Kozo

doi:10.1016/j.neuron.2013.12.015

Cited by 142 publications

(155 citation statements)

References 84 publications

(110 reference statements)

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“…In the future, it will be interesting to combine the analysis of intracellular organization using tagged marker proteins with long-term timelapse imaging in order to unravel changes in intracellular organization throughout all developmental stages in vivo. In vivo, it has been shown that excitatory cortical neurons form their axon either during their multipolar stage (de Anda et al, 2010;Hatanaka and Yamauchi, 2013;Namba et al, 2014;Sakakibara et al, 2014) or during their bipolar migrating phase (Noctor et al, 2004;Sakakibara et al, 2014). It thus seems that neurons can establish axonal polarity at different times, perhaps depending on their origin.…”

Section: Discussionmentioning

confidence: 99%

Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons

Gartner

Fornasiero

Valtorta

et al. 2014

Journal of Cell Science

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Final morphological polarization of neurons, with the development of a distinct axon and several dendrites, is preceded by phases where they have a non-polarized architecture. The earliest of these phases is that of the round neuron arising from the last mitosis. A second non-polarized stage corresponds to the bipolar neuron, with two morphologically identical neurites. Both phases have their distinctive relevance in the establishment of neuronal polarity. During the round cell stage, a decision is made as to where from the cell periphery a first neurite will form, thus creating the first sign of asymmetry. At the bipolar stage a decision is made as to which of the two neurites becomes the axon in neurons polarizing in vitro, and the leading edge in neurons in situ. In this study, we analysed cytoskeletal and membrane dynamics in cells at these two 'prepolarity' stages. By means of time lapse imaging in dissociated hippocampal neurons and ex vivo cortical slices, we show that both stages are characterized by polarized intracellular arrangements. However, the stages have distinct temporal hierarchies: polarized actin dynamics marks the site of first polarization in round cells, whereas polarized membrane dynamics precedes asymmetric growth in the bipolar stage.

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Section: Discussionmentioning

confidence: 99%

Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons

Gartner

Fornasiero

Valtorta

et al. 2014

Journal of Cell Science

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“…Time-lapse imaging of cortical slice cultures has revealed variability in the establishment of neuronal polarization in the developing neocortex. Almost 60% of MP cells first extend the trailing process (future axon) and then generate a leading process (future dendrite), whereas ∼30% of MP cells first generate a leading process and then extend the trailing process (Hatanaka and Yamauchi, 2013;Namba et al, 2014). The remaining 10% of MP cells form both processes simultaneously .…”

Section: Axon Versus Dendrite Initiation In Vivomentioning

confidence: 99%

Neuronal polarization

et al. 2015

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Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo.

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“…To determine when during these morphological changes neurons establish their post-mitotic identity, recently generated neurons were labeled with membrane bound GFP (F-FGP) in utero at E15. These cells were migrating into the CP of the developing mouse cortex at E18-E19 and have initiated axon extension ( Figure 1A and 1B [11,[19][20][21][22]), suggesting that the neuronal identity may be established during the migrating phase in the CP. Accordingly, electroporated cells in the CP, which are migrating to their final positions, have voltage-dependent currents characteristic of young neurons [11].…”

Section: Newly Born Neurons From Upper Cortical Layers Gradually Attamentioning

confidence: 99%

Cortical neurons gradually attain a post-mitotic state

et al. 2016

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Once generated, neurons are thought to permanently exit the cell cycle and become irreversibly differentiated. However, neither the precise point at which this post-mitotic state is attained nor the extent of its irreversibility is clearly defined. Here we report that newly born neurons from the upper layers of the mouse cortex, despite initiating axon and dendrite elongation, continue to drive gene expression from the neural progenitor tubulin α1 promoter (Tα1p). These observations suggest an ambiguous post-mitotic neuronal state. Whole transcriptome analysis of sorted upper cortical neurons further revealed that neurons continue to express genes related to cell cycle progression long after mitotic exit until at least post-natal day 3 (P3). These genes are however downregulated thereafter, associated with a concomitant upregulation of tumor suppressors at P5. Interestingly, newly born neurons located in the cortical plate (CP) at embryonic day 18-19 (E18-E19) and P3 challenged with calcium influx are found in S/G2/M phases of the cell cycle, and still able to undergo division at E18-E19 but not at P3. At P5 however, calcium influx becomes neurotoxic and leads instead to neuronal loss. Our data delineate an unexpected flexibility of cell cycle control in early born neurons, and describe how neurons transit to a post-mitotic state.

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Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex

Cited by 142 publications

References 84 publications

Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons

Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons

Neuronal polarization

Cortical neurons gradually attain a post-mitotic state

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