Maintenance of Wnt-3 expression in Purkinje cells of the mouse cerebellum depends on interactions with granule cells

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1277-1286 ◽  
Author(s):  
P.C. Salinas ◽  
C. Fletcher ◽  
N.G. Copeland ◽  
N.A. Jenkins ◽  
R. Nusse
Keyword(s):  
Cell Fate ◽  
Purkinje Cells ◽  
Granular Layer ◽  
Simple Structure ◽  
Granule Cells ◽  
Cell Populations ◽  
Specific Cell ◽  
External Granular Layer ◽  
Mouse Mutants ◽  
The Brain

Wnt genes encode secreted proteins implicated in cell fate changes during development. To define specific cell populations in which Wnt genes act, we have examined Wnt expression in the cerebellum. This part of the brain has a relatively simple structure and contains well-characterized cell populations. We found that Wnt-3 is expressed during development of the cerebellum and that expression is restricted to the Purkinje cell layer in the adult. Wnt-3 expression in Purkinje cells increases postnatally as granule cells start to make contacts with Purkinje cells. To investigate whether interactions with granule cells influence Wnt-3 expression in Purkinje cells, we examined gene expression in several mouse mutants, using the expression of En-2 to follow the fate of granule cells. In the weaver mutant, in which granule cells fail to migrate and subsequently die in the external granular layer, Wnt-3 expression was normal at postnatal day 15 (P15). At that time, some granule cells are still present in the external granular layer. At P28, however, when granule cells could no longer be detected, Wnt-3 expression was almost absent. In the meander tail mutant, in which the anterior cerebellar lobes lack granule cells, Wnt-3 expression was only detected in the normal posterior lobes. Since En genes are implicated in cell-cell interactions mediated by Wnt genes, we examined En-2/En-2 mutant mice, finding normal Wnt-3 expression, indicating that the effect of granule cells on the maintenance of Wnt-3 is not mediated by En-2. Our results show that Wnt-3 expression in Purkinje cells is modulated by their presynaptic granule cells at the time of neuronal maturation.

scholarly journals Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum

2021 ◽  
Vol 14 ◽  
Author(s):  
G. Giacomo Consalez ◽  
Daniel Goldowitz ◽  
Filippo Casoni ◽  
Richard Hawkes
Keyword(s):  
Granular Layer ◽  
Granule Cells ◽  
Review Article ◽  
Cell Type ◽  
External Granular Layer ◽  
Homogeneous Population ◽  
Multiple Phenotypes ◽  
Numerous Cell ◽  
Rhombic Lip ◽  
The Brain

Granule cells (GCs) are the most numerous cell type in the cerebellum and indeed, in the brain: at least 99% of all cerebellar neurons are granule cells. In this review article, we first consider the formation of the upper rhombic lip, from which all granule cell precursors arise, and the way by which the upper rhombic lip generates the external granular layer, a secondary germinal epithelium that serves to amplify the upper rhombic lip precursors. Next, we review the mechanisms by which postmitotic granule cells are generated in the external granular layer and migrate radially to settle in the granular layer. In addition, we review the evidence that far from being a homogeneous population, granule cells come in multiple phenotypes with distinct topographical distributions and consider ways in which the heterogeneity of granule cells might arise during development.

scholarly journals Efficient generation of reciprocal signals by inhibition

2012 ◽  
Vol 107 (9) ◽  
pp. 2453-2462 ◽  
Author(s):  
Sung-min Park ◽  
Esra Tara ◽  
Kamran Khodakhah
Keyword(s):  
Purkinje Cells ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Cell Activity ◽  
Common Mechanism ◽  
Input Output ◽  
Firing Rates ◽  
Neuronal Computation ◽  
The Brain

Reciprocal activity between populations of neurons has been widely observed in the brain and is essential for neuronal computation. The different mechanisms by which reciprocal neuronal activity is generated remain to be established. A common motif in neuronal circuits is the presence of afferents that provide excitation to one set of principal neurons and, via interneurons, inhibition to a second set of principal neurons. This circuitry can be the substrate for generation of reciprocal signals. Here we demonstrate that this equivalent circuit in the cerebellar cortex enables the reciprocal firing rates of Purkinje cells to be efficiently generated from a common set of mossy fiber inputs. The activity of a mossy fiber is relayed to Purkinje cells positioned immediately above it by excitatory granule cells. The firing rates of these Purkinje cells increase as a linear function of mossy fiber, and thus granule cell, activity. In addition to exciting Purkinje cells positioned immediately above it, the activity of a mossy fiber is relayed to laterally positioned Purkinje cells by a disynaptic granule cell → molecular layer interneuron pathway. Here we show in acutely prepared cerebellar slices that the input-output relationship of these laterally positioned Purkinje cells is linear and reciprocal to the first set. A similar linear input-output relationship between decreases in Purkinje cell firing and strength of stimulation of laterally positioned granule cells was also observed in vivo. Use of interneurons to generate reciprocal firing rates may be a common mechanism by which the brain generates reciprocal signals.

Influence of experimentally induced agranularity on the synaptogenesis of serotonin nerve terminals in rat cerebellar cortex

1979 ◽  
Vol 206 (1162) ◽  
pp. 133-138 ◽  
Keyword(s):  
Cerebellar Cortex ◽  
Granular Layer ◽  
Granule Cells ◽  
Absolute Number ◽  
External Granular Layer ◽  
X Ray ◽  
Synaptic Contacts ◽  
Cellular Environment ◽  
Normal Controls ◽  
Synaptic Remodelling

The serotonin (5-HT) innervation of the posterior vermis was studied by high resolution radioautography in both normal and X-ray-induced agranular rat cerebella, following 3 h topical superfusion with 10 -4 M 3 H-5-HT. In the normal cerebellar cortex, 5-HT axonal varicosities are scarce and only rarely exhibit the membrane differentiations character­izing synaptic contacts. In the agranular cerebellum, 5-HT terminals ap­pear to have a much higher density than in normal controls, although their absolute number may not be significantly different when the import­ant reduction in volume of this experimental cerebellum is taken into account. These terminals frequently show typical synaptic contacts. Most of them are established on the branchlet spines of Purkinje cell dendrites, but some are also observed on the shafts of Golgi cell dendrites. The 5-HT innervation of the cerebellar cortex thus undergoes important changes in the absence of granule cells. It is suggested that these modifications may be part of the general reorganization process of the cerebellar circuitry consequent on the early destruction of the external granular layer. This new example of synaptic remodelling could imply that the formation of cerebellar connectivity is modulated, to a certain extent, by the local cellular environment.

scholarly journals An updated investigation on the dromedary camel cerebellum (Camelus dromedarius) with special insight into the distribution of calcium-binding proteins

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abdelraheim H. Attaai ◽  
Ahmed E. Noreldin ◽  
Fatma M. Abdel-maksoud ◽  
Manal T. Hussein
Keyword(s):  
Purkinje Cells ◽  
Calcium Binding ◽  
Binding Proteins ◽  
Granular Layer ◽  
Granule Cells ◽  
Molecular Layer ◽  
Calcium Binding Proteins ◽  
Dromedary Camel ◽  
Cell Layers ◽  
Calbindin D

AbstractStudying the cerebella of different animals is important to expand the knowledge about the cerebellum. Studying the camel cerebellum was neglected even though the recent research in the middle east and Asia. Therefore, the present study was designed to achieve a detailed description of the morphology and the cellular organization of the camel cerebellum. Because of the high importance of the calcium ions as a necessary moderator the current work also aimed to investigate the distribution of calcium binding proteins (CaBP) such as calbindin D-28K (CB), parvalbumin (PV) and calretinin (CR) in different cerebellar cells including the non-traditional neurons. The architecture of camel cerebellum, as different mammals, consists of the medulla and three layered-cortex. According to our observation the cells in the granular layer were not crowded and many spaces were observed. CB expression was the highest by Purkinje cells including their dendritic arborization. In addition to its expression by the inhibitory interneurons (basket, stellate and Golgi neurons), it is also expressed by the excitatory granule cells. PV was expressed by Purkinje cells, including their primary arborization, and by the molecular layer cells. CR immunoreactivity (-ir) was obvious in almost all cell layers with varying degrees, however a weak or any expression by the Purkinje cells. The molecular layer cells and the Golgi and the non traditional large neurons of the granular layer showed the strongest CR-ir. Granule neurons showed moderate immunoreactivity for CB and CR. In conclusion, the results of the current study achieved a complete map for the neurochemical organization of CaBP expression and distribution by different cells in the camel cerebellum.

scholarly journals Cerebellar nuclei neurons dictate cortical growth through developmental scaling of presynaptic Purkinje cells

2018 ◽  
Author(s):  
Ryan T. Willett ◽  
Alexandre Wojcinski ◽  
N. Sumru Bayin ◽  
Zhimin Lao ◽  
Daniel Stephen ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Granule Cells ◽  
Cell Types ◽  
Cerebellar Nuclei ◽  
Conditional Knockout ◽  
Neural Systems ◽  
Specific Cell ◽  
Embryonic Loss ◽  
Local Circuits ◽  
Rhombic Lip

AbstractEfficient function of neural systems requires the production of specific cell types in the correct proportions. Here we report that reduction of the earliest born neurons of the cerebellum, excitatory cerebellar nuclei neurons (eCN), results in a subsequent reduction in growth of the cerebellar cortex due to an accompanying loss of their presynaptic target Purkinje cells. Conditional knockout of the homeobox genes En1 and En2 (En1/2) in the rhombic lip-derived eCN and granule cell precursors leads to embryonic loss of a subset of medial eCN and cell non-autonomous and location specific loss of Purkinje cells, with subsequent proportional scaling down of cortex growth. We propose that subsets of eCN dictate the survival of their specific Purkinje cell partners, and in turn sonic hedgehog secreted by Purkinje cells scales the expansion of granule cells and interneurons to produce functional local circuits and the proper folded morphology of the cerebellum.

Interaction of granule, Purkinje and inferior olivary neurons in Lurcher chimaeric mice

Development ◽  
1982 ◽  
Vol 68 (1) ◽  
pp. 87-98
Author(s):  
Richard Wetts ◽  
Karl Herrup
Keyword(s):  
Purkinje Cells ◽  
Granule Cells ◽  
Gene Action ◽  
Primary Site ◽  
Cell Marker ◽  
Wild Type ◽  
Wild Type Embryo ◽  
A Cell ◽  
Inferior Olivary ◽  
The Brain

Heterozygous lurcher (+/Lc) mutant mice lose 100% of their Purkinje cells (PCs), 90% of their granule cells, and 75% of their inferior olivary neurons. In order to determine the primary site of Lc gene action, lurcher↔ wild-type aggregation chimaeras were produced. The cerebella of the three chimaeras examined were intermediate or normal in size compared to +/Lc and wild-type cerebella. The PCs were reduced in number. Using the β-glucuronidase locus (Gus) as a cell marker, all of the PCs present were identified as having descended from the wild-type embryo. It appears that all of the +/Lc PCs degenerated. Hence, the Lc gene acts directly on PCs to cause their degeneration. The inferior olivary nuclei of the chimaeras seemed to have fewer neurons than wild-type but more than +/Lc animals. As revealed by β-glucuronidase histochemistry, both +/+and +/Lc cells were present, and the ratio of genotypes was similar to the ratio seen in other regions of the brain. The evidence suggests that the death of olivary neurons in lurcher is secondary to another defect, probably the loss of PCs. β-glucuronidase is not an accutate cell marker for granule cells, and so no conclusion concerning the action of the Lc gene on granule cells could be made with these chimaeras.

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.

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