Regulation of survival in adult hippocampal and glioblastoma stem cell lineages by the homeodomain-only protein HOP

doi:10.1186/1749-8104-3-13

Neural Development

Volume 3

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De Toni A
Zbinden M
Epstein JA
Altaba AR
Prochiantz A
Caillé I

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Zbinden M
Epstein JA
Altaba AR
Prochiantz A
Caillé I
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Research article

Regulation of survival in adult hippocampal and glioblastoma stem cell lineages by the homeodomain-only protein HOP

Arianna De Toni¹^* , Marie Zbinden²^* , Jonathan A Epstein³ , Ariel Ruiz i Altaba² , Alain Prochiantz¹^,4 and Isabelle Caillé¹^,5

¹UMR CNRS 8542, ENS, rue d'Ulm, 75005 Paris, France

²University of Geneva Medical School, 8542 CMU, rue Michel Servet, CH-1211 Geneva 4, Switzerland

³Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Curie Boulevard, Philadelphia, Pennsylvania 19104, USA

⁴Collège de France, place Marcelin Berthelot, 75231 Paris Cedex 05, France

⁵UFR de Biologie, Université Denis Diderot, 75013 Paris, France

author email corresponding author email* Contributed equally

Neural Development 2008, 3:13doi:10.1186/1749-8104-3-13


Published:	28 May 2008

Abstract

Background

Homeodomain proteins play critical roles in shaping the development of the embryonic central nervous system in mammals. After birth, neurogenic activities are relegated to stem cell niches, which include the subgranular layer of the dentate gyrus of the hippocampus. Here, we have analyzed the function of HOP (Homeodomain only protein) in this stem cell niche and in human glioblastomas.

Results

We find that HOP is strongly expressed by radial astrocytes of the dentate gyrus in mice, which are stem cells that give rise to hippocampal granular neurons throughout adulthood. Deletion or down-regulation of HOP results in a decrease of apoptosis of these stem cells without changes in proliferation, and in an increase in the number of newly formed granule neurons. We also find that human glioblastomas largely lack HOP expression and that reintroduction of HOP function in glioma cells cultured as gliomaspheres leads to enhanced apoptosis in a subset of cases. In these cells, HOP function decreases clonogenicity.

Conclusion

These data suggest that HOP participates in the regulation of the adult mouse hippocampal stem cell niche by negatively affecting cell survival. In addition, HOP may work as a tumor suppressor in a subset of glioblastomas. HOP function thus appears to be critical in the adult brain in a region of continued plasticity, and its deregulation may contribute to disease.