title: An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma.
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.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: De Smaele
authors.forename: Caterina
authors.initials: C
authors.lastname: Fragomeli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.forename: Marianna
authors.initials: M
authors.lastname: Pelloni
authors.forename: Agnese
authors.initials: A
authors.lastname: Po
authors.forename: Gianluca
authors.initials: G
authors.lastname: Canettieri
authors.forename: Sonia
authors.initials: S
authors.lastname: Coni
authors.forename: Lucia
authors.initials: L
authors.lastname: Di Marcotullio
authors.forename: Azzura
authors.initials: A
authors.lastname: Greco
authors.forename: Marta
authors.initials: M
authors.lastname: Moretti
authors.forename: Concezio
authors.initials: C
authors.lastname: Di Rocco
authors.forename: Simona
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: Marella
authors.initials: M
authors.lastname: Maroder
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D012097:Repressor Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D000071676:Zinc Finger Protein GLI1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C477059:Insm1 protein, mouse; C498272:Nhlh1 protein, mouse; C509239:SHH protein, human