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.

scholarly journals Cerebellar granule cells contain a membrane mitogen for cultured Schwann cells.

1989 ◽  
Vol 108 (2) ◽  
pp. 607-611 ◽  
Author(s):  
P W Mason ◽  
J W Bigbee ◽  
G H DeVries
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Cultures ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Proteoglycan Synthesis ◽  
Cerebellar Granule ◽  
Mitogenic Signal

Proliferation of Schwann cells is one of the first events that occurs after contact with a growing axon. To further define the distribution and properties of this axonal mitogen, we have (a) cocultured cerebellar granule cells, which lack glial ensheathment in vivo with Schwann cells; and (b) exposed Schwann cell cultures to isolated granule cell membranes. Schwann cells cocultured with granule cells had a 30-fold increase in the labeling index over Schwann cells cultured alone, suggesting that the mitogen is located on the granule cell surface. Inhibition of granule cell proteoglycan synthesis caused a decrease in the granule cells' ability to stimulate Schwann cell proliferation. Membranes isolated from cerebellar granule cells when added to Schwann cell cultures caused a 45-fold stimulation in [3H]thymidine incorporation. The granule cell mitogenic signal was heat and trypsin sensitive and did not require lysosomal processing by Schwann cells to elicit its proliferative effect. The ability of granule cells and their isolated membranes to stimulate Schwann cell proliferation suggests that the mitogenic signal for Schwann cells is a ubiquitous factor present on all axons regardless of their ultimate state of glial ensheathment.

Intrauterine Growth Restriction Affects Cerebellar Granule Cells in the Developing Guinea Pig Brain

2018 ◽  
Vol 40 (2) ◽  
pp. 162-174 ◽  
Author(s):  
Mary Tolcos ◽  
Annie McDougall ◽  
Amy Shields ◽  
Yoonyoung Chung ◽  
Rachael O’Dowd ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Purkinje Cells ◽  
Granule Cell ◽  
Intrauterine Growth Restriction ◽  
Granular Layer ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Growth Restriction ◽  
Cerebellar Granule ◽  
Intrauterine Growth

Intrauterine growth restriction (IUGR) can lead to adverse neurodevelopmental sequelae in postnatal life. However, the effects of IUGR on the cerebellum are still to be fully elucidated. A major determinant of growth and development of the cerebellum is proliferation and subsequent migration of cerebellar granule cells. Our objective was to determine whether IUGR, induced by chronic placental insufficiency (CPI) in guinea pigs, results in abnormal cerebellar development due to deficits suggestive of impaired granule cell proliferation and/or migration. CPI was induced by unilateral ligation of the uterine artery at mid-gestation, producing growth-restricted (GR) foetuses at 52 and 60 days of gestation (dg), and neonates at 1 week postnatal age (term approx. 67 dg). Controls were from sham-operated animals. In GR foetuses compared with controls at 52 dg, the external granular layer (EGL) width and internal granular layer (IGL) area were similar. In GR foetuses compared with controls at 60 dg: (a) the EGL width was greater (p < 0.005); (b) the IGL area was smaller (p < 0.005); (c) the density of Ki67-negative (postmitotic) granule cells in the EGL was greater (p < 0.01); (d) the somal area of Purkinje cells was reduced (p < 0.005), and (e) the linear density of Bergmann glia was similar. The EGL width in GR foetuses at 60 dg was comparable to that of 52 dg control and GR foetuses. The pattern of p27-immunoreactivity in the EGL was the inverse of Ki67-immunoreactivity at both foetal ages; there was no difference between control and GR foetuses at either age in the width of p27-immunoreactivity, or in the percentage of the EGL width that it occupied. In the molecular layer of GR neonates compared with controls there was an increase in the areal density of granule cells (p < 0.05) and in the percentage of migrating to total number of granule cells (p < 0.01) at 1 week but not at 60 dg (p > 0.05). Thus, we found no specific evidence that IUGR affects granule cell proliferation, but it alters the normal program of migration to the IGL and, in addition, the development of Purkinje cells. Such alterations will likely affect the development of appropriate circuitry and have implications for cerebellar function.

The Role of Galanin in Cerebellar Granule Cell Migration in the Early Postnatal Mouse during Normal Development and After Injury

2021 ◽  
pp. JN-RM-0900-15
Author(s):  
Yutaro Komuro ◽  
Ludovic Galas ◽  
Yury M. Morozov ◽  
Jennifer K. Fahrion ◽  
Emilie Raoult ◽  
...  
Keyword(s):  
Cell Migration ◽  
Granule Cell ◽  
Normal Development ◽  
Cerebellar Granule Cell ◽  
Cerebellar Granule

BDNF stimulates migration of cerebellar granule cells

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1435-1442 ◽  
Author(s):  
Paul R. Borghesani ◽  
Jean Michel Peyrin ◽  
Robyn Klein ◽  
Joshua Rubin ◽  
Alexandre R. Carter ◽  
...  
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cell Layer ◽  
Time Lapse ◽  
Granule Cell Layer ◽  
Boyden Chamber ◽  
Cerebellar Granule ◽  
Proliferative Zone ◽  
On Line

During development of the nervous system, neural progenitors arise in proliferative zones, then exit the cell cycle and migrate away from these zones. Here we show that migration of cerebellar granule cells out of their proliferative zone, the external granule cell layer (EGL), is impaired in Bdnf–/– mice. The reason for impaired migration is that BDNF directly and acutely stimulates granule cell migration. Purified Bdnf–/– granule cells show defects in initiation of migration along glial fibers and in Boyden chamber assays. This phenotype can be rescued by exogenous BDNF. Using time-lapse video microscopy we find that BDNF is acutely motogenic as it stimulates migration of individual granule cells immediately after addition. The stimulation of migration reflects both a chemokinetic and chemotactic effect of BDNF. Collectively, these data demonstrate that BDNF is directly motogenic for granule cells and provides a directional cue promoting migration from the EGL to the internal granule cell layer (IGL). Movies available on-line

The role of calcium and cyclic nucleotide signaling in cerebellar granule cell migration under normal and pathological conditions

2014 ◽  
Vol 75 (4) ◽  
pp. 369-387 ◽  
Author(s):  
Yutaro Komuro ◽  
Ludovic Galas ◽  
Alexis Lebon ◽  
Emilie Raoult ◽  
Jennifer K. Fahrion ◽  
...  
Keyword(s):  
Cell Migration ◽  
Granule Cell ◽  
Cyclic Nucleotide ◽  
Cerebellar Granule Cell ◽  
Cerebellar Granule ◽  
Pathological Conditions ◽  
Nucleotide Signaling

scholarly journals Role of Calcineurin Signaling in Membrane Potential-Regulated Maturation of Cerebellar Granule Cells

2009 ◽  
Vol 29 (9) ◽  
pp. 2938-2947 ◽  
Author(s):  
M. Okazawa ◽  
H. Abe ◽  
M. Katsukawa ◽  
K. Iijima ◽  
T. Kiwada ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule ◽  
Calcineurin Signaling
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