Heterogeneity of glycinergic and gabaergic interneurons in the granule cell layer of mouse cerebellum

Sonic hedgehog promotes proliferation of developing cerebellar granule cells. As sonic hedgehog is expressed in the cerebellum throughout life it is not clear why proliferation occurs only in the early postnatal period and only in the external granule cell layer. We asked whether heparan sulfate proteoglycans might regulate sonic hedgehog-induced proliferation and thereby contribute to the specialized proliferative environment of the external granule cell layer. We identified a conserved sequence within sonic hedgehog that is essential for binding to heparan sulfate proteoglycans, but not for binding to the receptor patched. Sonic hedgehog interactions with heparan sulfate proteoglycans promote maximal proliferation of postnatal day 6 granule cells. By contrast, proliferation of less mature granule cells is not affected by sonic hedgehog-proteoglycan interactions. The importance of proteoglycans for proliferation increases during development in parallel with increasing expression of the glycosyltransferase genes, exostosin 1 and exostosin 2. These data suggest that heparan sulfate proteoglycans, synthesized by exostosins, may be critical determinants of granule cell proliferation.

Download Full-text

BDNF stimulates migration of cerebellar granule cells

Development ◽

10.1242/dev.129.6.1435 ◽

2002 ◽

Vol 129 (6) ◽

pp. 1435-1442 ◽

Cited By ~ 3

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

Download Full-text

Dentate Gyrus Immaturity in Schizophrenia

The Neuroscientist ◽

10.1177/1073858418824072 ◽

2019 ◽

Vol 25 (6) ◽

pp. 528-547 ◽

Cited By ~ 5

Author(s):

Ayda Tavitian ◽

Wei Song ◽

Hyman M. Schipper

Keyword(s):

Animal Models ◽

Dentate Gyrus ◽

Granule Cell ◽

Cell Layer ◽

Current Theory ◽

Position Paper ◽

Granule Cell Layer ◽

Molecular Profile ◽

Rodent Models

Hippocampal abnormalities have been heavily implicated in the pathophysiology of schizophrenia. The dentate gyrus of the hippocampus was shown to manifest an immature molecular profile in schizophrenia subjects, as well as in various animal models of the disorder. In this position paper, we advance a hypothesis that this immature molecular profile is accompanied by an identifiable immature morphology of the dentate gyrus granule cell layer. We adduce evidence for arrested maturation of the dentate gyrus in the human schizophrenia-affected brain, as well as multiple rodent models of the disease. Implications of this neurohistopathological signature for current theory regarding the development of schizophrenia are discussed.

Download Full-text