Dataset Information

Ectopic overexpression of engrailed-2 in cerebellar Purkinje cells causes restricted cell loss and retarded external germinal layer development at lobule junctions.

ABSTRACT: Members of the En and Wnt gene families seem to play a key role in the early specification of the brain territory that gives rise to the cerebellum, the midhindbrain junction. To analyze the possible continuous role of the En and Wnt signaling pathway in later cerebellar patterning and function, we expressed En-2 ectopically in Purkinje cells during late embryonic and postnatal cerebellar development. As a result of this expression, the cerebellum is greatly reduced in size, and Purkinje cell numbers throughout the cerebellum are reduced by more than one-third relative to normal animals. Detailed analysis of both adult and developing cerebella reveals a pattern of selectivity to the loss of Purkinje cells and other cerebellar neurons. This is observed as a general loss of prominence of cerebellar fissures that is highlighted by a total loss of sublobular fissures. In contrast, mediolateral patterning is generally only subtly affected. That En-2 overexpression selectively affects Purkinje cells in the transition zone between lobules is evidenced by direct observation of selective Purkinje cell loss in certain fissures and by the observation that growth and migration of the external germinal layer (EGL) is selectively retarded in the deep fissures during early postnatal development. Thus, in addition to demonstrating the critical role of Purkinje cells in the generation and migration of granule cells, the heterogeneous distribution of cellular effects induced by ectopic En expression suggests a relatively late morphogenetic role for this and other segment polarity proteins, mainly oriented at lobule junctions.

SUBMITTER: Baader SL

PROVIDER: S-EPMC6792618 | biostudies-literature | 1998 Mar

REPOSITORIES: biostudies-literature

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Ectopic overexpression of engrailed-2 in cerebellar Purkinje cells causes restricted cell loss and retarded external germinal layer development at lobule junctions.

Baader S L SL Sanlioglu S S Berrebi A S AS Parker-Thornburg J J Oberdick J J

The Journal of neuroscience : the official journal of the Society for Neuroscience 19980301 5

Members of the En and Wnt gene families seem to play a key role in the early specification of the brain territory that gives rise to the cerebellum, the midhindbrain junction. To analyze the possible continuous role of the En and Wnt signaling pathway in later cerebellar patterning and function, we expressed En-2 ectopically in Purkinje cells during late embryonic and postnatal cerebellar development. As a result of this expression, the cerebellum is greatly reduced in size, and Purkinje cell nu ...[more]

PMID: 9465001

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Project description:ObjectiveCerebellar transcranial direct current stimulation (ctDCS) is challenging due to the complexity of the cerebellar structure which is reflected by the well-known variability in ctDCS effects. Therefore, our objective is to present a freely available computational modeling pipeline for cerebellar lobules' optimal stimulation (CLOS).MethodsCLOS can optimize lobule-specific electric field distribution following finite element analysis (FEA) using freely available computational modeling pipelines. We modeled published ctDCS montages with 5 cm × 5 cm anode placed 3 cm lateral to inion, and the same sized cathode was placed on the: (1) contralateral supra-orbital area (called Manto montage), and (2) buccinators muscle (called Celnik montage). Also, a published (3) 4×1 HD-ctDCS electrode montage was modeled. We also investigated the effects of the subject-specific head model versus Colin 27 average head model on lobule-specific electric field distribution. Three-way analysis of variance (ANOVA) was used to determine the effects of lobules, montage, and head model on the electric field distribution. The differences in lobule-specific electric field distribution across different freely available computational pipelines were also evaluated using subject-specific head model. We also presented an application of our computational pipeline to optimize a ctDCS electrode montage to deliver peak electric field at the cerebellar lobules VII-IX related to ankle function.ResultsEta-squared effect size after three-way ANOVA for electric field strength was 0.05 for lobule, 0.00 for montage, 0.04 for the head model, 0.01 for lobule?montage interaction, 0.01 for lobule? head model interaction, and 0.00 for montage?head model interaction. The electric field strength of both the Celnik and the Manto montages affected the lobules Crus I/II, VIIb, VIII, and IX of the targeted cerebellar hemisphere where Manto montage had a spillover to the contralateral cerebellar hemisphere. The 4×1 HD-ctDCS montage primarily affected the lobules Crus I/II of the targeted cerebellar hemisphere. All three published ctDCS montages were found to be not optimal for ankle function (lobules VII-IX), so we presented a novel HD-ctDCS electrode montage.DiscussionOur freely available CLOS pipeline can be leveraged to optimize electromagnetic stimulation to target cerebellar lobules related to different cognitive and motor functions.

Dataset Information

Ectopic overexpression of engrailed-2 in cerebellar Purkinje cells causes restricted cell loss and retarded external germinal layer development at lobule junctions.

Publications

Ectopic overexpression of engrailed-2 in cerebellar Purkinje cells causes restricted cell loss and retarded external germinal layer development at lobule junctions.

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