Bergmann Glia Function in Granule Cell Migration During Cerebellum Development

Xu, Haiwei; Yang, Yang; Tang, Xi; Zhao, Meina; Liang, Fucheng; Xu, Pei; Hou, Baoke; Xing, Yan; Bao, Xiaofeng; Fan, Xiaotang

doi:10.1007/s12035-013-8405-y

Cited by 74 publications

(65 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bergmann glia are located in the Purkinje cell layer and extend processes to the pial surface; these glial cells guide the migration of granule cells during development (38). In our VWM mice, Bergmann glia were displaced to the molecular layer and showed withdrawal of endfeet at the pial surface, increased process thickening, lateral branching, and strong GFAPδ immunoreactivity.…”

Section: Discussionmentioning

confidence: 58%

Astrocytes are central in the pathomechanisms of vanishing white matter

Dooves¹,

Bugiani²,

Postma³

et al. 2016

Journal of Clinical Investigation

124

229

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 58%

Astrocytes are central in the pathomechanisms of vanishing white matter

Dooves¹,

Bugiani²,

Postma³

et al. 2016

Journal of Clinical Investigation

124

229

View full text Add to dashboard Cite

“…We found no change in the expression of Shh , considered to be the main driver of granule cell proliferation; however, given the lack of changes in cell proliferation, this is not surprising. Additional factors known to be involved in granule cell-Bergman glia interactions, including profilin1 [47] , cell adhesion molecule L1 (L1-CAM; [48] ), and α-dystroglycan [48] should be examined in future studies.…”

Section: The Effect Of Iugr On Molecular Factors That Regulate Granulmentioning

confidence: 99%

Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum

et al. 2017

View full text Add to dashboard Cite

Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR.

show abstract

“…GENES & DEVELOPMENTadjacent to the Purkinje neurons, and they project radial fibers into the EGL to provide scaffolds for GNP migration (Chanas-Sacre et al 2000;D'Arca et al 2010;Xu et al 2013). Because we observed cre-recombinase activity in BG of both mutant mouse strains, NF1 deficiency in BGs could, in principle, account for or contribute to the observed cerebellar defects, including the migration phenotype.…”

Section: Nf1 Regulates Cerebellar Developmentmentioning

confidence: 99%

NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development

et al. 2014

View full text Add to dashboard Cite

Cerebellar development is regulated by a coordinated spatiotemporal interplay between granule neuron progenitors (GNPs), Purkinje neurons, and glia. Abnormal development can trigger motor deficits, and more recent data indicate important roles in aspects of memory, behavior, and autism spectrum disorders (ASDs). Germline mutation in the NF1 tumor suppressor gene underlies Neurofibromatosis type 1, a complex disease that enhances susceptibility to certain cancers and neurological disorders, including intellectual deficits and ASD. The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering and structure. Remarkably, neonatal administration of inhibitors of the ERK pathway reversed the morphological defects. Thus, our findings establish a critical cell-autonomous role for the NF1-RAS-ERK pathway in the appropriate regulation of cerebellar development and provide a basis for using neonatal ERK inhibitor-based therapies to treat NF1-induced cerebellar disorders.

show abstract

Bergmann Glia Function in Granule Cell Migration During Cerebellum Development

Cited by 74 publications

References 103 publications

Astrocytes are central in the pathomechanisms of vanishing white matter

Astrocytes are central in the pathomechanisms of vanishing white matter

Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum

NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development

Contact Info

Product

Resources

About