Neuronal polarization

Takano, Tetsuya; Xu, Chengpei; Funahashi, Yasuhiro; Namba, Tsuneo; Kaibuchi, Kozo

doi:10.1242/dev.114454

Cited by 124 publications

(113 citation statements)

References 65 publications

(103 reference statements)

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“…Pyramidal neurons first extend multiple minor processes and are called multipolar (MP) cells in intermediate zone (IZ). These MP cells subsequently transform into bipolar (BP) cells with a trailing process and a leading process, which finally develop into an axon and a dendrite, respectively 2, 3 . BP cells are completely polarized and migrate toward the cortical plate (CP).…”

Section: Resultsmentioning

confidence: 99%

“…We previously reported that Rho-kinase phosphorylates and inactivates p190RhoGAP, thereby leading to sustained activation of RhoA 56 . Rho-kinase also inactivates Rac1 through phosphorylation of Par3 and Rac GEFs (STEF/Tiam) 1, 3, 57 . Following Rho-kinase activation by long-range inhibitory signaling, the activated RhoA may be sustained and diffused by Rho-kinase-dependent inactivation of RhoGAP, ultimately guaranteeing neuronal polarity through multiple pathways in minor neurites.…”

Section: Discussionmentioning

confidence: 99%

“…We previously hypothesized that polarized neurons use a robust long-range inhibitory mechanism to generate only one axon, thereby determining dendritic specification 1, 3 . Once axonal fate is determined, the growing nascent axon of a stage 3 neuron is speculated to send a stronger long-range inhibitory signal to the other minor neurites, preventing the formation of unnecessary axons.…”

Section: Introductionmentioning

confidence: 99%

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Discovery of long-range inhibitory signaling to ensure single axon formation

et al. 2017

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A long-standing question in neurodevelopment is how neurons develop a single axon and multiple dendrites from common immature neurites. Long-range inhibitory signaling from the growing axon is hypothesized to prevent outgrowth of other immature neurites and to differentiate them into dendrites, but the existence and nature of this inhibitory signaling remains unknown. Here, we demonstrate that axonal growth triggered by neurotrophin-3 remotely inhibits neurite outgrowth through long-range Ca2+ waves, which are delivered from the growing axon to the cell body. These Ca2+ waves increase RhoA activity in the cell body through calcium/calmodulin-dependent protein kinase I. Optogenetic control of Rho-kinase combined with computational modeling reveals that active Rho-kinase diffuses to growing other immature neurites and inhibits their outgrowth. Mechanistically, calmodulin-dependent protein kinase I phosphorylates a RhoA-specific GEF, GEF-H1, whose phosphorylation enhances its GEF activity. Thus, our results reveal that long-range inhibitory signaling mediated by Ca2+ wave is responsible for neuronal polarization.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Discovery of long-range inhibitory signaling to ensure single axon formation

et al. 2017

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“…The polarization of neuron cells characterizes the formation of axons and dendrites in neuron cells and is crucial for neuronal functionality 54, 55 . Many extra – and intracellular processes are responsible for the establishment and maintenance of cell polarity, such as protein diffusion and scaffold formation, secretory pathways, and ion channel activity 56 .…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-mediated piezoelectric differentiation of neuron-like PC12 cells on PVDF membranes

Hoop

Chen

Ferrari

et al. 2017

Sci Rep

154

134

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Electrical and/or electromechanical stimulation has been shown to play a significant role in regenerating various functionalities in soft tissues, such as tendons, muscles, and nerves. In this work, we investigate the piezoelectric polymer polyvinylidene fluoride (PVDF) as a potential substrate for wireless neuronal differentiation. Piezoelectric PVDF enables generation of electrical charges on its surface upon acoustic stimulation, inducing neuritogenesis of PC12 cells. We demonstrate that the effect of pure piezoelectric stimulation on neurite generation in PC12 cells is comparable to the ones induced by neuronal growth factor (NGF). In inhibitor experiments, our results indicate that dynamic stimulation of PVDF by ultrasonic (US) waves activates calcium channels, thus inducing the generation of neurites via a cyclic adenosine monophosphate (cAMP)-dependent pathway. This mechanism is independent from the well-studied NGF induced mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) pathway. The use of US, in combination with piezoelectric polymers, is advantageous since focused power transmission can occur deep into biological tissues, which holds great promise for the development of non-invasive neuroregenerative devices.

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“…Neuronal cells, which have unique characteristics with a distinct morphology, critically require a well-regulated system of synthesis and degradation of proteins at the time of development, as well as in later life stages (Yi and Ehlers, 2007; Takano et al, 2015). They maintain a polar shape, in order to develop a functional neuronal circuitry (Tahirovic and Bradke, 2009).…”

Section: Key Questions and Future Prospectivementioning

confidence: 99%

E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

Upadhyay

Joshi

Amanullah

et al. 2017

Front. Mol. Neurosci.

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Cells regularly synthesize new proteins to replace old or damaged proteins. Deposition of various aberrant proteins in specific brain regions leads to neurodegeneration and aging. The cellular protein quality control system develop various defense mechanisms against the accumulation of misfolded and aggregated proteins. The mechanisms underlying the selective recognition of specific crucial protein or misfolded proteins are majorly governed by quality control E3 ubiquitin ligases mediated through ubiquitin-proteasome system. Few known E3 ubiquitin ligases have shown prominent neurodevelopmental functions, but their interactions with different developmental proteins play critical roles in neurodevelopmental disorders. Several questions are yet to be understood properly. How E3 ubiquitin ligases determine the specificity and regulate degradation of a particular substrate involved in neuronal proliferation and differentiation is certainly the one, which needs detailed investigations. Another important question is how neurodevelopmental E3 ubiquitin ligases specifically differentiate between their versatile range of substrates and timing of their functional modulations during different phases of development. The premise of this article is to understand how few E3 ubiquitin ligases sense major molecular events, which are crucial for human brain development from its early embryonic stages to throughout adolescence period. A better understanding of these few E3 ubiquitin ligases and their interactions with other potential proteins will provide invaluable insight into disease mechanisms to approach toward therapeutic interventions.

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Neuronal polarization

Cited by 124 publications

References 65 publications

Discovery of long-range inhibitory signaling to ensure single axon formation

Discovery of long-range inhibitory signaling to ensure single axon formation

Ultrasound-mediated piezoelectric differentiation of neuron-like PC12 cells on PVDF membranes

E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

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