1206 The role of neurotrophin for the neurite extension and cell migration of cerebellar granule cells in vitro

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.

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

10.1101/357541 ◽

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.

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Two-Photon Photoactivation of Rubi-Gaba for Studying the Role of the Antisecretory Factor in the Modulation of the GABAA Receptor in Rat Cerebellar Granule Cells In Vitro

Biophysical Journal ◽

10.1016/j.bpj.2020.11.569 ◽

2021 ◽

Vol 120 (3) ◽

pp. 55a

Author(s):

Virginia Bazzurro ◽

Elena Gatta ◽

Elena Angeli ◽

Aroldo Cupello ◽

Stefan Lange ◽

...

Keyword(s):

Gabaa Receptor ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Cerebellar Granule ◽

Two Photon ◽

Antisecretory Factor

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Methyl iodide toxicity in rat cerebellar granule cells in vitro: the role of glutathione

Toxicology ◽

10.1016/s0300-483x(99)00099-2 ◽

1999 ◽

Vol 139 (1-2) ◽

pp. 27-37 ◽

Cited By ~ 19

Author(s):

Mark P Chamberlain ◽

Nicholas C Sturgess ◽

Edward A Lock ◽

Celia J Reed

Keyword(s):

Methyl Iodide ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Cerebellar Granule

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1811100115 ◽

2018 ◽

Vol 115 (42) ◽

pp. 10556-10563 ◽

Cited By ~ 12

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.

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