Suppressors of Hedgehog signaling

Linking aberrant development of neural progenitors and tumorigenesis

Lucia Di Marcotullio, Elisabetta Ferretti, Enrico De Smaele, Isabella Screpanti, Alberto Gulino

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Subversion of signals that physiologically suppress Hedgehog pathway results in aberrant neural progenitor development and medulloblastoma, a malignancy of the cerebellum. The Hedgehog antagonist RENKCTD11 maps to chromosome 17p13.2 and is involved in the withdrawal of the Hedgehog signaling at the granule cell progenitor transition from the outer to the inner external germinal layers, thus promoting growth arrest and differentiation. Deletion of chromosome 17p, the most frequent genetic lesion observed in this tumor, is responsible for the loss of function of RENKCTD11, resulting in upregulated Hedgehog signaling and medulloblastoma. Persistence of signals that limit Hedgehog activity is also associated with malignancy. Hedgehog signaling- induced downregulation of ErbB4 receptor expression is attenuated in medulloblastoma subsets in which the extent of Hedgehog pathway activity is limited, thus favoring the accumulation of ErbB4 with imbalanced alternative splice CYT-1 isoform over the CYT-2. This is responsible for both Neuregulin ligand-induced CYT-1-dependent prosurvival activity and loss of CYT-2-mediated growth arrest.

Original languageEnglish
Pages (from-to)193-204
Number of pages12
JournalMolecular Neurobiology
Volume34
Issue number3
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Medulloblastoma
Carcinogenesis
Neuregulins
Neoplasms
Chromosome Deletion
Growth
Cerebellum
Protein Isoforms
Stem Cells
Down-Regulation
Chromosomes
Ligands

Keywords

  • Cerebellum
  • ErbB4
  • Gli
  • Granule cell progenitors
  • Hedgehog
  • Medulloblastoma
  • Neural stem cells
  • REN

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Suppressors of Hedgehog signaling : Linking aberrant development of neural progenitors and tumorigenesis. / Di Marcotullio, Lucia; Ferretti, Elisabetta; De Smaele, Enrico; Screpanti, Isabella; Gulino, Alberto.

In: Molecular Neurobiology, Vol. 34, No. 3, 12.2006, p. 193-204.

Research output: Contribution to journalArticle

Di Marcotullio, L, Ferretti, E, De Smaele, E, Screpanti, I & Gulino, A 2006, 'Suppressors of Hedgehog signaling: Linking aberrant development of neural progenitors and tumorigenesis', Molecular Neurobiology, vol. 34, no. 3, pp. 193-204. https://doi.org/10.1385/MN:34:3:193
Di Marcotullio, Lucia ; Ferretti, Elisabetta ; De Smaele, Enrico ; Screpanti, Isabella ; Gulino, Alberto. / Suppressors of Hedgehog signaling : Linking aberrant development of neural progenitors and tumorigenesis. In: Molecular Neurobiology. 2006 ; Vol. 34, No. 3. pp. 193-204.
@article{65c82fc69bc047c9b80177c6af38e2f9,
title = "Suppressors of Hedgehog signaling: Linking aberrant development of neural progenitors and tumorigenesis",
abstract = "Subversion of signals that physiologically suppress Hedgehog pathway results in aberrant neural progenitor development and medulloblastoma, a malignancy of the cerebellum. The Hedgehog antagonist RENKCTD11 maps to chromosome 17p13.2 and is involved in the withdrawal of the Hedgehog signaling at the granule cell progenitor transition from the outer to the inner external germinal layers, thus promoting growth arrest and differentiation. Deletion of chromosome 17p, the most frequent genetic lesion observed in this tumor, is responsible for the loss of function of RENKCTD11, resulting in upregulated Hedgehog signaling and medulloblastoma. Persistence of signals that limit Hedgehog activity is also associated with malignancy. Hedgehog signaling- induced downregulation of ErbB4 receptor expression is attenuated in medulloblastoma subsets in which the extent of Hedgehog pathway activity is limited, thus favoring the accumulation of ErbB4 with imbalanced alternative splice CYT-1 isoform over the CYT-2. This is responsible for both Neuregulin ligand-induced CYT-1-dependent prosurvival activity and loss of CYT-2-mediated growth arrest.",
keywords = "Cerebellum, ErbB4, Gli, Granule cell progenitors, Hedgehog, Medulloblastoma, Neural stem cells, REN",
author = "{Di Marcotullio}, Lucia and Elisabetta Ferretti and {De Smaele}, Enrico and Isabella Screpanti and Alberto Gulino",
year = "2006",
month = "12",
doi = "10.1385/MN:34:3:193",
language = "English",
volume = "34",
pages = "193--204",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press Inc.",
number = "3",

}

TY - JOUR

T1 - Suppressors of Hedgehog signaling

T2 - Linking aberrant development of neural progenitors and tumorigenesis

AU - Di Marcotullio, Lucia

AU - Ferretti, Elisabetta

AU - De Smaele, Enrico

AU - Screpanti, Isabella

AU - Gulino, Alberto

PY - 2006/12

Y1 - 2006/12

N2 - Subversion of signals that physiologically suppress Hedgehog pathway results in aberrant neural progenitor development and medulloblastoma, a malignancy of the cerebellum. The Hedgehog antagonist RENKCTD11 maps to chromosome 17p13.2 and is involved in the withdrawal of the Hedgehog signaling at the granule cell progenitor transition from the outer to the inner external germinal layers, thus promoting growth arrest and differentiation. Deletion of chromosome 17p, the most frequent genetic lesion observed in this tumor, is responsible for the loss of function of RENKCTD11, resulting in upregulated Hedgehog signaling and medulloblastoma. Persistence of signals that limit Hedgehog activity is also associated with malignancy. Hedgehog signaling- induced downregulation of ErbB4 receptor expression is attenuated in medulloblastoma subsets in which the extent of Hedgehog pathway activity is limited, thus favoring the accumulation of ErbB4 with imbalanced alternative splice CYT-1 isoform over the CYT-2. This is responsible for both Neuregulin ligand-induced CYT-1-dependent prosurvival activity and loss of CYT-2-mediated growth arrest.

AB - Subversion of signals that physiologically suppress Hedgehog pathway results in aberrant neural progenitor development and medulloblastoma, a malignancy of the cerebellum. The Hedgehog antagonist RENKCTD11 maps to chromosome 17p13.2 and is involved in the withdrawal of the Hedgehog signaling at the granule cell progenitor transition from the outer to the inner external germinal layers, thus promoting growth arrest and differentiation. Deletion of chromosome 17p, the most frequent genetic lesion observed in this tumor, is responsible for the loss of function of RENKCTD11, resulting in upregulated Hedgehog signaling and medulloblastoma. Persistence of signals that limit Hedgehog activity is also associated with malignancy. Hedgehog signaling- induced downregulation of ErbB4 receptor expression is attenuated in medulloblastoma subsets in which the extent of Hedgehog pathway activity is limited, thus favoring the accumulation of ErbB4 with imbalanced alternative splice CYT-1 isoform over the CYT-2. This is responsible for both Neuregulin ligand-induced CYT-1-dependent prosurvival activity and loss of CYT-2-mediated growth arrest.

KW - Cerebellum

KW - ErbB4

KW - Gli

KW - Granule cell progenitors

KW - Hedgehog

KW - Medulloblastoma

KW - Neural stem cells

KW - REN

UR - http://www.scopus.com/inward/record.url?scp=33847084412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847084412&partnerID=8YFLogxK

U2 - 10.1385/MN:34:3:193

DO - 10.1385/MN:34:3:193

M3 - Article

VL - 34

SP - 193

EP - 204

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 3

ER -