scholarly journals N-Cadherin Provides a Cis and Trans Ligand for Astrotactin that Functions in Glial-Guided Neuronal Migration

2018 ◽  
Author(s):  
Zachi Horn ◽  
Hourinaz Behesti ◽  
Mary E. Hatten
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Neuronal Migration ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Mutant Form ◽  
Cerebellar Granule ◽  
Neuronal Receptor ◽  
Cis And Trans

AbstractPrior studies demonstrate that Astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell-cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss of Cdh2 in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronal Cdh2, and more severe migration defects occurred after a conditional loss of glial Cdh2. Expression of a mutant form of ASTN1 that does not bind CDH2, in granule cells, also slowed migration. Moreover, in vitro chimeras of granule cells and glia showed impaired neuron-glia attachment in the absence of glial, but not neuronal, Cdh2. Thus, cis and trans bindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron-glial bridge complex that promotes glial-guided neuronal migration.

scholarly journals N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration

2018 ◽  
Vol 115 (42) ◽  
pp. 10556-10563 ◽  
Author(s):  
Zachi Horn ◽  
Hourinaz Behesti ◽  
Mary E. Hatten
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Neuronal Migration ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Mutant Form ◽  
Cerebellar Granule ◽  
Neuronal Receptor ◽  
Cis And Trans

Prior studies demonstrate that astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell–cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss of Cdh2 in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronal Cdh2, and more severe migration defects occurred after a conditional loss of glial Cdh2. Expression in granule cells of a mutant form of ASTN1 that does not bind CDH2 also slowed migration. Moreover, in vitro chimeras of granule cells and glia showed impaired neuron–glia attachment in the absence of glial, but not neuronal, Cdh2. Thus, cis and trans bindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron–glial bridge complex that promotes glial-guided neuronal migration.

Role of Pax6 in development of the cerebellar system

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3585-3596 ◽  
Author(s):  
D. Engelkamp ◽  
P. Rashbass ◽  
A. Seawright ◽  
V. van Heyningen
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Long Distance ◽  
Cerebellar Granule ◽  
Precerebellar Nuclei ◽  
Rhombic Lip

Post-mitotic neurons generated at the rhombic lip undertake long distance migration to widely dispersed destinations, giving rise to cerebellar granule cells and the precerebellar nuclei. Here we show that Pax6, a key regulator in CNS and eye development, is strongly expressed in rhombic lip and in cells migrating away from it. Development of some structures derived from these cells is severely affected in Pax6-null Small eye (Pax6(Sey)/Pax6(Sey)) embryos. Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos. Three of the five precerebellar nuclei fail to form correctly. In the cerebellum the pre-migratory granule cell sub-layer and fissures are absent. Some granule cells are found in ectopic positions in the inferior colliculus which may result from the complete absence of Unc5h3 expression in Pax6(Sey)/Pax6(Sey) granule cells. Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3.

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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