Prolonged Glial Expression of Sox4 in the CNS Leads to Architectural Cerebellar Defects and Ataxia

Hoser, Melanie; Baader, Stephan L.; Bösl, Michael R.; Ihmer, Alice; Wegner, Michael; Sock, Elisabeth

doi:10.1523/jneurosci.1384-07.2007

Cited by 47 publications

(42 citation statements)

References 50 publications

(71 reference statements)

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“…In GFAP-Sox4 transgenic mice, the characteristic layering was not achieved. Indeed fissures and lobules did not form, and neuronal subtypes failed to reach their proper destination and aggregated in clusters (Hoser et al, 2007); in this mutant, radial glia failed to migrate to the normal position and did not extend radial fibers to the pial surface.…”

Section: Defects Of Cerebellum Fissuresmentioning

confidence: 81%

“…The studies on transgenic mice (Hoser et al, 2007) showing cerebellar anomalies in the foliation process suggest that defects in the formation of folia and fissures are under genetic control. Anomalies have been frequently found over extended breeding cycles for a given breeder (Ezerman and Kromer, 1985;Ramos et al, 2008) as well as in B6 mice, a strain widely used for the generation of knockout mice (Tanaka and Marunouchi, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, architectural cerebellar defects were also found to result from a failure of Bergman glia to undergo correct differentiation in the developing cerebellum (Hoser et al, 2007). Studies on human neuronal migration disorders demonstrate how defects in migration as well as cell proliferation, survival, and differentiation may contribute to the malformation genesis (Ross and Walsh, 2001).…”

mentioning

confidence: 99%

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Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

Cerri¹,

Piccolini²,

Bernocchi³

2010

The Anatomical Record

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A natural defect in rat cerebellum postnatal development has been found in the fissura prima, consisting in various complex configurations of the cerebellar layers. We investigated the genesis of fissure malformations through immunoreactions for PCNA, GFAP, GABAA a6, and calbindin to label proliferating cells of the external granular layer (egl), radial glial fibers, mature granule cells, and Purkinje cells, respectively. Results on critical stages of rat postnatal development provided interesting evidences on how the malformation develops in fissures prima and secunda. Early (postnatal day 10) at the site of malformation, the Bergmann radial glia was often retracted and showed distortions and irregular running. The interruption of GFAP-positive radial glial fibers could fit in with the presence of clusters of PCNA-unlabeled cells in the sites of fusion of the egl; the clusters of cells are granule cells since their soma is labeled by GABAA a6. Moreover, an altered migration of granule cell precursors to the internal granular layer was evident which, in turn, affected Purkinje cell differentiation and the growth of their dendrites. In summary, the changed relationship among glial fiber morphology, granule cell migration, and Purkinje cell differentiation suggests how the Bergmann glial fibers have a basic role in the foliation process, being the driving physical force in directing migration of the granule cells at the base of fissure. Anat Rec, 293:492-501, 2010. V V C 2010 Wiley-Liss, Inc.

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Section: Defects Of Cerebellum Fissuresmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

Cerri¹,

Piccolini²,

Bernocchi³

2010

The Anatomical Record

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“…The downregulation of these miRNAs had many effects, but the most predominant function is increasing the metastatic potential via upregulation of genes involved in motility and proliferation. Specifically, miR-335 loss leads to altered expression of genes such as SOX4, neuropilin 1 and semaphoring 3C, which control progenitor cell development and migration (Hoser et al, 2007). Studies on miR-126 show the context-specific actions in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

et al. 2010

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Metastasis in breast cancer carries a disproportionately worse prognosis than localized primary disease. To identify microRNAs (miRNA) involved in metastasis, the expression of 254 miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231), metastatic disease to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231). A brain-seeking variant of this cell line (231-BR) was used additionally in validation studies. Twenty miRNAs were upregulated and seven were downregulated in metastatic cancer cells compared with TMD-231 cells. The expression of the tumor suppressor miRNAs let-7 and miR-22 was consistently downregulated in metastatic cancer cells. These metastatic cells expressed higher levels of putative/proven miR-22 target oncogenes ERBB3, CDC25C and EVI-1. Introduction of miR-22 into cancer cells reduced the levels of ERBB3 and EVI-1 as well as phospho-AKT, an EVI-1 downstream target. The miR-22 primary transcript is located in the 5 0 -untranslated region of an open reading frame C17orf91, and the promoter/enhancer of C17orf91 drives miR-22 expression. We observed elevated C17orf91 expression in non-basal subtype compared with basal subtype breast cancers. In contrast, elevated expression of EVI-1 was observed in basal subtype and was associated with poor outcome in estrogen receptor-negative breast cancer patients. These results suggest that metastatic cancer cells increase specific oncogenic signaling proteins through downregulation of miRNAs. Identifying such metastasisspecific oncogenic pathways may help to manipulate tumor behavior and aid in the design of more effective targeted therapies.

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“…20 ), the c-Mer tyrosine kinase (MERTK) 21 and the phospholipase PLCB1 ( ref. 22 ); as well as in cell migration, such as tenascin C (TNC) 23 and the SRY-box containing transcription factor SOX4 (refs 24,25 ).…”

Section: Mir-335 Regulates a Set Of Metastasis Genesmentioning

confidence: 99%

Endogenous human microRNAs that suppress breast cancer metastasis

Tavazoie

Alarcón

Oskarsson

et al. 2008

Nature

1,724

1,427

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A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 inhibits metastatic cell invasion. miR-335 regulates a set of genes whose collective expression in a large cohort of human tumours is associated with risk of distal metastasis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcription factor SOX4 and extracellular matrix component tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer.Although metastasis is the overwhelming cause of mortality in patients with solid tumours, our understanding of its molecular and cellular determinants is limited 1-3 . Transcriptional profiling has revealed sets of genes, or `signatures', for which expression in primary tumours correlates with metastatic relapse or poor survival 4 . Some of these genes endow cancer cells with a more invasive phenotype, enhanced angiogenic and intravasation activity, the ability to exit from the circulation, or an ability to modify the metastasis microenvironment 5,6 . Such gene sets are thus providing numerous candidate mediators of metastasis to be validated through functional and clinical studies. Much less insight, however, has been gained into the

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Prolonged Glial Expression of Sox4 in the CNS Leads to Architectural Cerebellar Defects and Ataxia

Cited by 47 publications

References 50 publications

Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

Endogenous human microRNAs that suppress breast cancer metastasis

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