An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma.
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.
De Smaele
Enrico
E
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Fragomeli
Caterina
C
Ferretti
Elisabetta
E
Pelloni
Marianna
M
Po
Agnese
A
Canettieri
Gianluca
G
Coni
Sonia
S
Di Marcotullio
Lucia
L
Greco
Azzura
A
Moretti
Marta
M
Di Rocco
Concezio
C
Pazzaglia
Simona
S
Maroder
Marella
M
Screpanti
Isabella
I
Giannini
Giuseppe
G
Gulino
Alberto
A
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
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