Abstract
Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh) pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH) activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Cerebellar Neoplasms / genetics*
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Cerebellum / drug effects
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Cerebellum / growth & development*
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Cerebellum / metabolism
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DNA-Binding Proteins / genetics*
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Gene Expression / drug effects
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Gene Expression Regulation, Developmental*
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Gene Expression Regulation, Neoplastic*
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Hedgehog Proteins / metabolism*
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Hedgehog Proteins / pharmacology
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Humans
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Medulloblastoma / genetics*
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Mice
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Molecular Sequence Data
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Oncogene Proteins / metabolism
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Organogenesis / genetics*
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Repressor Proteins
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Trans-Activators / metabolism
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Transcription Factors / genetics*
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Tumor Cells, Cultured
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Zinc Finger Protein GLI1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Hedgehog Proteins
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Insm1 protein, mouse
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Nhlh1 protein, mouse
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Oncogene Proteins
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Repressor Proteins
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SHH protein, human
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Trans-Activators
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Transcription Factors
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Zinc Finger Protein GLI1