Local Control of Granule Cell Generation by Cerebellar Purkinje Cells

Smeyne, Richard J.; Chu, Tzong‐Shinn; Lewin, Anne; Bian, Feng; Şanlıoğlu, Salih; Kunsch, Charles; Sa, Lira; Oberdick, John

doi:10.1006/mcne.1995.1019

Cited by 200 publications

(175 citation statements)

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“…To generate L7-B-50/GAP-43 hybrid transgene, the B-50/GAP-43 open reading frame (ORF) was inserted in a vector named L7⌬AUG, essentially as described by Smeyne et al (1995). This vector includes 1 kb of the L7 promoter, the four exons and three introns, and 200 bp downstream of the TGA stop codon of the L7 gene, from which the normal and all potential downstream ATGs were removed (Smeyne et al, 1995). The B-50/GAP-43 ORF was inserted into the unique BamHI site in the fourth exon of the L7 gene (see Fig.…”

Section: Methodsmentioning

confidence: 99%

Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants

et al. 1997

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B-50/GAP-43 is a nervous tissue-specific protein, the expression of which is associated with axon growth and regeneration. Its overexpression in transgenic mice produces spontaneous axonal sprouting and enhances induced remodeling in several neuron populations (Aigner et al., 1995;Holtmaat et al., 1995). We examined the capacity of this protein to increase the regenerative potential of injured adult central axons, by inducing targeted B-50/GAP-43 overexpression in Purkinje cells, which normally show poor regenerative capabilities. Thus, transgenic mice were produced in which B-50/GAP-43 overexpression was driven by the Purkinje cell-specific L7 promoter. Uninjured transgenic Purkinje cells displayed normal morphology, indicating that transgene expression does not modify the normal phenotype of these neurons. By contrast, after axotomy numerous transgenic Purkinje cells exhibited profuse sprouting along the axon and at its severed end. Nevertheless, despite these growth phenomena, which never occurred in wild-type mice, the severed transgenic axons were not able to regenerate, either spontaneously or into embryonic neural or Schwann cell grafts placed into the lesion site. Finally, although only a moderate Purkinje cell loss occurred in wild-type cerebella after axotomy, a considerable number of injured transgenic neurons degenerated, but they could be partially rescued by the different transplants placed into the lesion site. Thus, B-50/GAP-43 overexpression substantially modifies Purkinje cell response to axotomy, by inducing growth processes and decreasing their resistance to injury. However, the presence of this protein is not sufficient to enable these neurons to accomplish a full program of axon regeneration.

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Section: Methodsmentioning

confidence: 99%

Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants

et al. 1997

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“…In particular, it has been demonstrated that these steps are actively controlled by mitogenic factors secreted by PCs. Indeed, the relative number of granule cells is reduced in animal models characterized by a primary PC degeneration [109][110][111], whereas if the loss of PCs occurs later in postnatal period (as in the pcd mutant mouse) the granule cell layer appears near normal [112,111]. Shh produced by PCs is the most efficacious mitogen acting on granule cell development.…”

Section: Shh and Granule Cellsmentioning

confidence: 99%

Sonic hedgehog patterning during cerebellar development

Luca

Cerrato

Fucà

et al. 2015

Cell. Mol. Life Sci.

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Abstract:Robust evidence in literature indicates that the morphogenic factor Sonic Hedgehog (Shh) actively orchestrates several aspects of cerebellar development and maturation. During embryogenesis Shh signalling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Purkinje cell (PC)-secreted Shh sustains the amplification of neurogenic niches active during postnatal development: the external granular layer (EGL) and the prospective white matter (PWM) where excitatory granule cells and inhibitory interneurons, respectively, are produced. In addition, Shh signalling acts on Bergmann glia differentiation and during development sustains cerebellar foliation. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying the role of this ligand in the development of different cerebellar phenotypes. Keywords: Shh, mitogen, differentiation, cerebellum.Authors declare no conflict of interest. AbstractRobust evidence in literature indicates that the morphogenic factor Sonic Hedgehog (Shh) actively orchestrates several aspects of cerebellar development and maturation. During embryogenesis Shh

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“…This could generate asymmetry in the cellular cytoskeleton, affecting cell polarity and orientation of the cleavage spindle during cell division. Second, signaling molecules that promote GCP proliferation and differentiation in the EGL have been suggested to be secreted from meningeal cells, the precursors themselves, and from Purkinje cells (Barakat et al, 1981;Hatten, 1985;Gao et al, 1991;Smeyne et al, 1995;Klein et al, 2001). Cell-ECM interactions could help to recruit secreted signaling molecules locally into the meningeal basement membranes.…”

Section: Integrins Ln and Shhmentioning

confidence: 99%

β1-Integrins Are Critical for Cerebellar Granule Cell Precursor Proliferation

Blaess¹,

Graus‐Porta²,

Belvindrah³

et al. 2004

J. Neurosci.

116

113

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We have previously shown that mice with a CNS restricted knock-out of the integrin ␤1 subunit gene (Itgb1-CNSko mice) have defects in the formation of lamina and folia in the cerebral and cerebellar cortices that are caused by disruption of the cortical marginal zones. Cortical structures in postnatal and adult Itgb1-CNSko animals are also reduced in size, but the mechanism that causes the size defect has remained unclear. We now demonstrate that proliferation of granule cell precursors (GCPs) is severely affected in the developing cerebellum of Itgb1-CNSko mice. In the absence of ␤1 expression, GCPs lose contact with laminin in the meningeal basement membrane, cease proliferating, and differentiate prematurely. In vitro studies provide evidence that ␤1 integrins act at least in part cell autonomously in GCPs to regulate their proliferation. Previous studies have shown that sonic hedgehog (Shh)-induced GCP proliferation is potentiated by the integrin ligand laminin. We show that Shh directly binds to laminin and that laminin-Shh induced cell proliferation is dependent on ␤1 integrin expression in GCPs. Taken together, these data are consistent with a model in which ␤1 integrin expression in GCPs is required to recruit a laminin-Shh complex to the surface of GCPs and to subsequently modulate the activity of signaling pathways that regulate proliferation.

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Local Control of Granule Cell Generation by Cerebellar Purkinje Cells

Cited by 200 publications

References 0 publications

Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants

Targeted Overexpression of the Neurite Growth-Associated Protein B-50/GAP-43 in Cerebellar Purkinje Cells Induces Sprouting after Axotomy But Not Axon Regeneration into Growth-Permissive Transplants

Sonic hedgehog patterning during cerebellar development

β1-Integrins Are Critical for Cerebellar Granule Cell Precursor Proliferation

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