scholarly journals Tissue specificity and regulation of the N-terminal diversity of reticulon 3

2004 ◽  
Vol 385 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Franck DI SCALA ◽  
Luc DUPUIS ◽  
Christian GAIDDON ◽  
Marc DE TAPIA ◽  
Natasa JOKIC ◽  
...  
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Granule Neurons ◽  
Cerebellar Granule ◽  
Preferential Expression ◽  
Protein Levels ◽  
The Central Nervous System ◽  
Cerebellum Development ◽  
Promoter Usage

Over the last few years, the widely distributed family of reticulons (RTNs) is receiving renewed interest because of the implication of RTN4/Nogo in neurite regeneration. Four genes were identified in mammals and are referred to as RTN1, 2, 3 and the neurite outgrowth inhibitor RTN4/Nogo. In the present paper, we describe the existence of five new isoforms of RTN3 that differ in their N-termini, and analysed their tissue distribution and expression in neurons. We redefined the structure of human and murine rtn3 genes, and identified two supplementary exons that may generate up to seven putative isoforms arising by alternative splicing or differential promoter usage. We confirmed the presence of five of these isoforms at the mRNA and protein levels, and showed their preferential expression in the central nervous system. We analysed rtn3 expression in the cerebellum further, and observed increased levels of several of the RTN3 isoforms during cerebellum development and during in vitro maturation of cerebellar granule cells. This pattern of expression paralleled that shown by RTN4/Nogo isoforms. Specifically, RTN3A1 expression was down-regulated upon cell death of cerebellar granule neurons triggered by potassium deprivation. Altogether, our results demonstrate that the rtn3 gene generates multiple isoforms varying in their N-termini, and that their expression is tightly regulated in neurons. These findings suggest that RTN3 isoforms may contribute, by as yet unknown mechanisms, to neuronal survival and plasticity.

scholarly journals Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wenqin Luo ◽  
Guan Ning Lin ◽  
Weichen Song ◽  
Yu Zhang ◽  
Huadong Lai ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Granule Neurons ◽  
Cerebellar Granule ◽  
Granule Neuron ◽  
Proliferation And Differentiation ◽  
Single Cell Rna Sequencing ◽  
Cerebellar Cells

Abstract Background Cerebellar neurogenesis involves the generation of large numbers of cerebellar granule neurons (GNs) throughout development of the cerebellum, a process that involves tight regulation of proliferation and differentiation of granule neuron progenitors (GNPs). A number of transcriptional regulators, including Math1, and the signaling molecules Wnt and Shh have been shown to have important roles in GNP proliferation and differentiation, and deregulation of granule cell development has been reported to be associated with the pathogenesis of medulloblastoma. While the progenitor/differentiation states of cerebellar granule cells have been broadly investigated, a more detailed association between developmental differentiation programs and spatial gene expression patterns, and how these lead to differential generation of distinct types of medulloblastoma remains poorly understood. Here, we provide a comparative single-cell spatial transcriptomics analysis to better understand the similarities and differences between developing granule and medulloblastoma cells. Results To acquire an enhanced understanding of the precise cellular states of developing cerebellar granule cells, we performed single-cell RNA sequencing of 24,919 murine cerebellar cells from granule neuron-specific reporter mice (Math1-GFP; Dcx-DsRed mice). Our single-cell analysis revealed that there are four major states of developing cerebellar granule cells, including two subsets of granule progenitors and two subsets of differentiating/differentiated granule neurons. Further spatial transcriptomics technology enabled visualization of their spatial locations in cerebellum. In addition, we performed single-cell RNA sequencing of 18,372 cells from Patched+/− mutant mice and found that the transformed granule cells in medulloblastoma closely resembled developing granule neurons of varying differentiation states. However, transformed granule neuron progenitors in medulloblastoma exhibit noticeably less tendency to differentiate compared with cells in normal development. Conclusion In sum, our study revealed the cellular and spatial organization of the detailed states of cerebellar granule cells and provided direct evidence for the similarities and discrepancies between normal cerebellar development and tumorigenesis.

Tetrabromobisphenol A-induced depolarization of rat cerebellar granule cells: ex vivo and in vitro studies

Chemosphere ◽  
2019 ◽  
Vol 223 ◽  
pp. 64-73 ◽  
Author(s):  
Dominik Diamandakis ◽  
Elzbieta Zieminska ◽  
Marcin Siwiec ◽  
Krzysztof Tokarski ◽  
Elzbieta Salinska ◽  
...  
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Ex Vivo ◽  
In Vitro Studies ◽  
Tetrabromobisphenol A ◽  
Cerebellar Granule

K252a, a potent inhibitor of protein kinases, inhibits the migration of cerebellar granule cells in vitro

1995 ◽  
Vol 90 (1-2) ◽  
pp. 122-128 ◽  
Author(s):  
Satoshi Kobayashi ◽  
Kaoru Isa ◽  
Kensuke Hayashi ◽  
Hiroshi K. Inoue ◽  
Keiichi Uyemura ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Potent Inhibitor ◽  
Cerebellar Granule

scholarly journals Bone Morphogenetic Protein-6 Promotes Cerebellar Granule Neurons Survival by Activation of the MEK/ERK/CREB Pathway

2009 ◽  
Vol 20 (24) ◽  
pp. 5051-5063 ◽  
Author(s):  
Bruna Barneda-Zahonero ◽  
Alfredo Miñano-Molina ◽  
Nahuai Badiola ◽  
Rut Fadó ◽  
Xavier Xifró ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Neuroprotective Effect ◽  
High Potassium ◽  
Cerebellar Granule ◽  
Low Potassium ◽  
Creb Pathway

Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined the eventual role of BMPs on the survival of these neurons. Lack of depolarization causes CGC death by apoptosis in vivo, a phenomenon that is mimicked in vitro by deprivation of high potassium in cultured CGCs. We have found that BMP-6, but not BMP-7, is able to block low potassium–mediated apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an increase of Smad translocation to the nucleus, suggesting that the canonical pathway is not involved. By contrast, activation of the MEK/ERK/CREB pathway by BMP-6 is necessary for its neuroprotective effect, which involves inhibition of caspase activity and an increase in Bcl-2 protein levels. Other pathways involved in the regulation of CGC survival, such as the c-Jun terminal kinase and the phosphatidylinositol 3-kinase (PI3K)-Akt/PKB, were not affected by BMP-6. Moreover, failure of BMP-7 to activate the MEK/ERK/CREB pathway could explain its inability to protect CGCs from low potassium–mediated apoptosis. Thus, this study demonstrates that BMP-6 acting through the noncanonical MEK/ERK/CREB pathway plays a crucial role on CGC survival.

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