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

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.

• Authors: Arianna De Toni, Marie Zbinden, Jonathan A Epstein, Ariel Ruiz i Altaba, Alain Prochiantz, Isabelle Caillé
• Journal: Neural development (Neural Dev) Vol. 3 Pg. 13 (May 28 2008) ISSN: 1749-8104 [Electronic] England
• PMID: 18507846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HOPX protein, human
• Homeodomain Proteins
• Hop protein, mouse
• RNA, Small Interfering
• Tumor Suppressor Proteins

Topics

• Age Factors
• Animals
• Apoptosis (physiology)
• Astrocytes (cytology, physiology)
• Brain Neoplasms (pathology, physiopathology)
• Cell Division (physiology)
• Cell Line, Tumor
• Cell Lineage (physiology)
• Cell Survival (physiology)
• Dentate Gyrus (cytology, embryology, physiology)
• Gene Expression Regulation, Developmental
• Glioblastoma (pathology, physiopathology)
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Mice
• Mice, Knockout
• RNA, Small Interfering
• Stem Cells (cytology, physiology)
• Tumor Suppressor Proteins (genetics, metabolism)