scholarly journals GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Meghan Morgan-Smith ◽  
Yaohong Wu ◽  
Xiaoqin Zhu ◽  
Julia Pringle ◽  
William D Snider
Keyword(s):  
Signaling Pathways ◽  
Cortical Neurons ◽  
Apical Dendrite ◽  
Regulatory Proteins ◽  
Radial Migration ◽  
Tangential Migration ◽  
Mouse Mutants ◽  
Basal Dendrites ◽  
Dendritic Arbors ◽  
Gsk 3Β

GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.

scholarly journals Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

2012 ◽  
Vol 33 (7) ◽  
pp. 861-872 ◽  
Author(s):  
Ying Jin ◽  
Hai-juan Sui ◽  
Yan Dong ◽  
Qi Ding ◽  
Wen-hui Qu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Gsk 3Β

scholarly journals Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dong Won Kim ◽  
Kai Liu ◽  
Zoe Qianyi Wang ◽  
Yi Stephanie Zhang ◽  
Abhijith Bathini ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Gabaergic Neurons ◽  
Zona Incerta ◽  
Long Distance ◽  
Hypothalamic Neurons ◽  
Cortical Interneuron ◽  
Tangential Migration ◽  
Innate Behaviors

AbstractGABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such as Pvalb. Here, we show that Lhx6 is necessary for the survival of hypothalamic neurons. Dlx1/2, Nkx2-2, and Nkx2-1 are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.

scholarly journals BMP signaling and radial migration of cortical neurons

2017 ◽  
Vol 145 ◽  
pp. S115
Author(s):  
Nitin Agnihotri ◽  
Monika Saxena ◽  
Jonaki Sen
Keyword(s):  
Cortical Neurons ◽  
Bmp Signaling ◽  
Radial Migration

scholarly journals The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander GJ Skorput ◽  
Stephanie M Lee ◽  
Pamela WL Yeh ◽  
Hermes H Yeh
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Fetal Alcohol Spectrum Disorders ◽  
Behavioral Flexibility ◽  
Ethanol Exposure ◽  
Embryonic Mouse ◽  
Form And Function ◽  
Tangential Migration ◽  
And Function

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.

Pseudolaric acid B induces endometrial cancer Ishikawa cell apoptosis and inhibits metastasis through AKT-GSK-3β and ERK1/2 signaling pathways

2017 ◽  
Vol 28 (6) ◽  
pp. 603-612 ◽  
Author(s):  
Dan Wang ◽  
Yanqiu Tian ◽  
Wenhua Feng ◽  
Li Zhao ◽  
Mingyi Zhao ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Ishikawa Cell ◽  
Pseudolaric Acid B ◽  
Gsk 3Β

Cellular migration patterns in the developing mouse cerebral cortex

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 713-732 ◽  
Author(s):  
C.P. Austin ◽  
C.L. Cepko
Keyword(s):  
Cortical Neurons ◽  
Intermediate Zone ◽  
Cellular Migration ◽  
Three Dimensions ◽  
Cortical Plate ◽  
Cortical Cells ◽  
Migration Patterns ◽  
Embryonic Mouse ◽  
Radial Migration ◽  
Almost All

The migration patterns of embryonic mouse cortical cells were investigated using a replication-incompetent retrovirus vector (BAG). The lateral ventricles of embryonic day 12 mouse embryos were infected with BAG and brains were harvested 2, 3, 4 and 6 days after infection. The location and morphology of all infected cortical cells were recorded from serial sections of entire brains, which were then reconstructed in three dimensions. Examination of the distribution of labelled cells revealed that there were migration patterns characteristic of each medial-lateral domain of the cortex. In the medial and dorsal areas, migration was often radial, although tangential spread increased with survival time, in large part due to ramification of cells in the intermediate zone. In the dorsolateral and lateral areas of the cortex, radial migration was generally not observed. Rather, variable extents of tangential migration occurred, and often resulted in wide separation of cells in the cortical plate. Almost all of the cellular dispersion occurred in the intermediate zone, although a modest degree of dispersion also occurred within the cortical plate itself. Most dispersion occurred in the mediolateral plane, with relatively little dispersion along the anteroposterior axis. Though characteristic migration patterns could be defined, wide variability in the extents of radial migration and tangential separation of cells was seen. The patterns of migration paralleled the distribution of radial glial fibers in all areas, and are most likely a reflection of the role of this network in supporting the migration of cortical neurons. The extent and variability of cellular dispersion supports a lineage-independent mechanism of cortical column ontogenesis.

Anti-angiogenic effect of chebulagic acid involves inhibition of the VEGFR2- and GSK-3β-dependent signaling pathways

2017 ◽  
Vol 95 (5) ◽  
pp. 563-570 ◽  
Author(s):  
A.P. Athira ◽  
C.S. Abhinand ◽  
K. Saja ◽  
A. Helen ◽  
P. Reddanna ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathways ◽  
Umbilical Vein ◽  
Docking Studies ◽  
Cell Contact ◽  
Downstream Signaling ◽  
Chebulagic Acid ◽  
Inhibition Of Angiogenesis ◽  
Gsk 3Β ◽  
Umbilical Vein Endothelial Cells

Inhibition of angiogenesis is a useful strategy to prevent cancer growth by targeting new vessels that grow to nourish actively proliferating tumor cells. Endothelial cells can use a number of different pathways to cause angiogenesis, and each step in these pathways can be targeted. The use of multi-targeted drugs is gaining much importance in this scenario. Our previous results have shown that chebulagic acid (a benzopyran tannin present in the fruits of Terminalia chebula) has anti-angiogenic properties. Thus, this study was designed to examine the molecular mechanism for the anti-angiogenic effects of chebulagic acid. Results from our investigations using molecular docking studies and human umbilical vein endothelial cells in culture suggested that chebulagic acid inhibits both GSK-3β-dependent β-catenin phosphorylation (an important mediator of VE-cadherin–β-catenin signaling) and VEGFR2 phosphorylation, which is an important step in VEGF signaling. Chebulagic acid inhibits angiogenesis by blocking both the VEGF–VEGFR2 complex and cell–cell contact dependent downstream signaling pathways.

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