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. 2013 Jan 24:6:198.
doi: 10.3389/fnins.2012.00198. eCollection 2012.

Medulloblastoma or not? Crucial role in tumorigenesis of the timing of migration of cerebellar granule precursor cells, regulated by Nos2 and Tis21

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Medulloblastoma or not? Crucial role in tumorigenesis of the timing of migration of cerebellar granule precursor cells, regulated by Nos2 and Tis21

Stefano Farioli-Vecchioli et al. Front Neurosci. .
No abstract available

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Figures

Figure 1
Figure 1
Proposed models of plasticity and transformation of cerebellar granule precursor cells (GCPs) in response to Math1, Tis21, Nos2, Cxcl3, or Gap43. (A) Hypothetical model for the ambivalent role of Math1 (Atoh1) in tumorigenesis and differentiation; in a proliferative (Shh) environment Math1 favors tumorigenesis, while when GCPs are exposed to a differentiative signal (Tis21), Math1 may have a prodifferentiative action. Math1 and Id3 were not selected among the 344 genes whose expression is modified by Tis21-knockout in the report by Farioli-Vecchioli et al. (2012a), because of the stringent cut-off imposed on the statistical analysis. See Figure A1 for analysis of Math 1 and Id3 mRNA levels in GCPs of Tis21-null mice. (B) Epigenetically-regulated genes among the 344 Tis21-regulated genes, either Tis21-knockout-specific (pairwise comparison of Tis21KO vs. Tis21WT) or medulloblastoma-specific (pairwise comparison of Ptch1+/−/Tis21KO vs. Ptch1+/−/Tis21WT); see (Farioli-Vecchioli et al., 2012a) and Figure A1 for enrichment analysis. (C) Model of plasticity and transformation of GCPs, involving Cxcl3- and Gap43-induced migration (see text). EGL, external granular layer (surface of cerebellum); ML, molecular layer; IGL, internal granular layer.
Figure A1
Figure A1
(A) Math1 and Id3 mRNA expression values by real time PCR analysis performed in GCPs from 7-days-old mice of the four genotypes indicated. Math1 mRNA levels are reduced in GCPs of Tis21 knockout mice, either in a Patched1 wild-type background (Tis21KO vs. Tis21WT) or in a Patched1 heterozygous background (Ptch1+/−/Tis21KO vs. Ptch1+/−/Tis21WT). Mean ± SEM fold increases are from three independent experiments. TBP was used to normalize data. *P < 0.05, or **P < 0.01, Student's t-test. (B) Enrichment analysis to identify epigenetically-regulated genes among the Tis21-regulated genes. Among the 344 Tis21-regulated genes, either Tis21-knockout-specific (pairwise comparison of Tis21KO vs. Tis21WT) or medulloblastoma-specific (pairwise comparison of Ptch1+/−/Tis21KO vs. Ptch1+/−/Tis21WT; see Farioli-Vecchioli et al., 2012a) genes were selected whose product interacts with histone modifying factors [i.e., arginine N-methyltransferase 1 (Prmt1), or histone deacetylases] or whose expression is significantly affected by inhibitors of DNA methylases or histone deacetylases. Enrichment P values were obtained with Fisher's exact test.

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