Tis21 knock-out enhances the frequency of medulloblastoma in patched1 heterozygous mice by inhibiting the cxcl3-dependent migration of cerebellar neurons (Articolo in rivista)

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  • Tis21 knock-out enhances the frequency of medulloblastoma in patched1 heterozygous mice by inhibiting the cxcl3-dependent migration of cerebellar neurons (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1523/JNEUROSCI.0412-12.2012. (literal)
Alternative label
  • Stefano Farioli-Vecchioli; Irene Cinà; Manuela Ceccarelli; Laura Micheli; Luca Leonardi; Maria Teresa Ciotti; Marco De Bardi; Concezio Di Rocco; Roberto Pallini; Sebastiano Cavallaro; Felice Tirone (2012)
    Tis21 knock-out enhances the frequency of medulloblastoma in patched1 heterozygous mice by inhibiting the cxcl3-dependent migration of cerebellar neurons
    in The Journal of neuroscience
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Stefano Farioli-Vecchioli; Irene Cinà; Manuela Ceccarelli; Laura Micheli; Luca Leonardi; Maria Teresa Ciotti; Marco De Bardi; Concezio Di Rocco; Roberto Pallini; Sebastiano Cavallaro; Felice Tirone (literal)
Pagina inizio
  • 15547 (literal)
Pagina fine
  • 15564 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 32 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 44 (literal)
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Institute of Cell Biology and Neurobiology, National Research Council, Fondazione Santa Lucia, and Neuroimmunology and Flow Cytometry Unit, Fondazione Santa Lucia, 00143 Rome, Italy, Institute of Neurosurgery, Catholic University School of Medicine, 00168 Rome, Italy, and Functional Genomics Center, Institute of Neurological Sciences, National Research Council, 95125 Catania, Italy. (literal)
Titolo
  • Tis21 knock-out enhances the frequency of medulloblastoma in patched1 heterozygous mice by inhibiting the cxcl3-dependent migration of cerebellar neurons (literal)
Abstract
  • A failure in the control of proliferation of cerebellar granule neuron precursor cells (GCPs), located in the external granular layer (EGL) of the cerebellum, gives rise to medulloblastoma. To investigate the process of neoplastic transformation of GCPs, we generated a new medulloblastoma model by crossing Patched1 heterozygous mice, which develop medulloblastomas with low frequency, with mice lacking the Tis21 gene. Overexpression of Tis21 is known to inhibit proliferation and trigger differentiation of GCPs; its expression decreases in human medulloblastomas. Double-knock-out mice show a striking increase in the frequency of medulloblastomas and hyperplastic EGL lesions, formed by preneoplastic GCPs. Tis21 deletion does not affect the proliferation of GCPs but inhibits their differentiation and, chiefly, their intrinsic ability to migrate outside the EGL. This defect of migration may represent an important step in medulloblastoma formation, as GCPs, remaining longer in the EGL proliferative niche, may become more prone to transformation. By genome-wide analysis, we identified the chemokine Cxcl3 as a target of Tis21. Cxcl3 is downregulated in Tis21-null GCPs of EGL and lesions; addition of Cxcl3 to cerebellar slices rescues the defective migration of Tis21-null GCPs and, remarkably, reduces the area of hyperplastic lesions. As Tis21 activates Cxcl3 transcription, our results suggest that Tis21 induces migration of GCPs through Cxcl3, which may represent a novel target for medulloblastoma therapy. (literal)
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