scholarly journals Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation

1993 ◽  
Vol 122 (2) ◽  
pp. 443-450 ◽  
Author(s):  
D Lindholm ◽  
E Castrén ◽  
P Tsoulfas ◽  
R Kolbeck ◽  
M da P Berzaghi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Calcium Binding ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Granule Neurons ◽  
Cerebellar Granule ◽  
Neurotrophin 3

Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinje cells do not express NT-3 mRNA but do express trkC, the putative neuronal receptor for NT-3. Addition of recombinant NT-3 to cerebellar cultures from embryonic rat brain induces hypertrophy and neurite sprouting of Purkinje cells, and upregulates the mRNA encoding the calcium-binding protein, calbindin-28 kD. The present study demonstrates a novel interaction between cerebellar granule neurons and developing Purkinje cells in which NT-3 induced by T3 in the granule cells promotes Purkinje cell differentiation.

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.

Multisensory signals in single cerebellar granule cells in vivo

2009 ◽  
Vol 65 ◽  
pp. S20
Author(s):  
Taro Ishikawa ◽  
Misa Shimuta ◽  
Michael Hausser
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
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.

The absence of pleiotrophin modulates gene expression in the hippocampus in vivo and in cerebellar granule cells in vitro

2016 ◽  
Vol 75 ◽  
pp. 113-121 ◽  
Author(s):  
Celia González-Castillo ◽  
Daniel Ortuño-Sahagún ◽  
Carolina Guzmán-Brambila ◽  
Ana Laura Márquez-Aguirre ◽  
Rita Raisman-Vozari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule

Cerebellar granule cells transplanted in vivo can follow physiological and unusual migratory routes to integrate into the recipient cortex

2008 ◽  
Vol 30 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Ian Martin Williams ◽  
Barbara Carletti ◽  
Ketty Leto ◽  
Lorenzo Magrassi ◽  
Ferdinando Rossi
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule ◽  
Migratory Routes

scholarly journals The relationship between birth timing, circuit wiring, and physiological response properties of cerebellar granule cells

2021 ◽  
Vol 118 (23) ◽  
pp. e2101826118
Author(s):  
S. Andrew Shuster ◽  
Mark J. Wagner ◽  
Nathan Pan-Doh ◽  
Jing Ren ◽  
Sophie M. Grutzner ◽  
...  
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Cerebellar Nuclei ◽  
Birth Timing ◽  
Imaging Data ◽  
Cerebellar Granule ◽  
Virus Tracing

Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project. To determine the role birth timing plays in GrC wiring and function, we developed genetic strategies to access early- and late-born GrCs. We initiated retrograde monosynaptic rabies virus tracing from control (birth timing unrestricted), early-born, and late-born GrCs, revealing the different patterns of mossy fiber input to GrCs in vermis lobule 6 and simplex, as well as to early- and late-born GrCs of vermis lobule 6: sensory and motor nuclei provide more input to early-born GrCs, while basal pontine and cerebellar nuclei provide more input to late-born GrCs. In vivo multidepth two-photon Ca2+ imaging of axons of early- and late-born GrCs revealed representations of diverse task variables and stimuli by both populations, with modest differences in the proportions encoding movement, reward anticipation, and reward consumption. Our results suggest neither organized parallel processing nor completely random organization of mossy fiber→GrC circuitry but instead a moderate influence of birth timing on GrC wiring and encoding. Our imaging data also provide evidence that GrCs can represent generalized responses to aversive stimuli, in addition to recently described reward representations.

In vivo analysis reveals different apoptotic pathways in pre- and postmigratory cerebellar granule cells of rabbit

2004 ◽  
Vol 60 (4) ◽  
pp. 437-452 ◽  
Author(s):  
Laura Lossi ◽  
Graziana Gambino ◽  
Silvia Mioletti ◽  
Adalberto Merighi
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule ◽  
In Vivo Analysis ◽  
Apoptotic Pathways

scholarly journals N-Methyl-d-Aspartate Evokes Rapid Net Depolymerization of Filamentous Actin in Cultured Rat Cerebellar Granule Cells

1997 ◽  
Vol 78 (2) ◽  
pp. 1135-1143 ◽  
Author(s):  
Spencer L. Shorte
Keyword(s):  
Actin Polymerization ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Receptor Activation ◽  
Cytochalasin D ◽  
Granule Neurons ◽  
Krebs Solution ◽  
Filamentous Actin ◽  
Normal Medium ◽  
Cerebellar Granule

Shorte, Spencer L. N-methyl-d-aspartate evokes rapid net depolymerization of filamentous actin in cultured rat cerebellar granule cells. J. Neurophysiol. 78: 1135–1143, 1997. Filamentous actin(F-actin) was measured in cultured rat cerebellum granule neurons with the use of fluorescently labeled phallotoxin as a site-specific probe for F-actin, and fluorescence microscopy. The averaged apparent intensity of soma-associated F-actin-derived fluorescence ( F app) was measured from fixed cells after incubation in either 1) normal Krebs solution containing 2 mM extracellular calcium ([Ca2+]ex) or 2) normal Krebs solution plus N-methyl-d-aspartate (NMDA) for 2 min immediately before fixation. NMDA (10, 50, and 100 μM) decreased F app to 63 ± 5% (mean ± SE), 53 ± 4%, and 47 ± 2%, respectively, of that measured from control cells. This effect was mimicked by treatment of cells with ionomycin. The ability of NMDA to reduce the F app in the presence of [Ca2+]ex was abolished when cells were maintained in [Ca2+]ex-free medium. Cells first treated with NMDA for 2 min and then left in normal medium for 30 min before fixation gave F app fluorescence similar to control values (91 ± 12%). However, if the F-actin polymerization inhibitor cytochalasin D was added to cells immediately after NMDA was removed, the F app did not recover with time (36 ± 3%). Cells treated for 30 min with cytochalasin D alone showed a small reduction in staining (∼20%). It is concluded that the actin polymerization state of rat cerebellar granule neurons is sensitive to changes in intracellular calcium, and that NMDA receptor activation evokes an initial rapid depolymerization of F-actin.

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