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Nuclear receptor binding protein 2 is induced during neural progenitor differentiation and affects cell survival
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2008 (English)In: Molecular and Cellular Neuroscience, ISSN 0890-8508, E-ISSN 1095-9327, Vol. 39, no 1, 32-9 p.Article in journal (Refereed) Published
Abstract [en]

We previously identified nuclear receptor binding protein 2 (NRBP2) in a screen for genes induced by differentiation of neural stem/progenitor cells. Here we show that during embryonic mouse brain development NRBP2 was expressed in the walls of the third and fourth ventricles, and in the hippocampus. In the adult brain, Purkinje cells of the cerebellum and neurons in the CA3 region of the hippocampus were main sites of NRBP2 expression. Analysis of a pediatric medulloblastoma showed that clusters of NRBP2 positive tumor cells co-expressed neurofilament, but not GFAP. Thus, NRBP2 was associated with neuronal differentiation both in normal and malignant brain tissue. We report that NRBP2 is a 55-60 kDa protein with mainly cytoplasmic location. In vitro, NRBP2 protein levels increased as neural stem/progenitor cells differentiated, and its down regulation by siRNA rendered neural progenitor cells more vulnerable to apoptosis. NRBP2 has no previously assigned function and our studies suggest a role for NRBP2 in neural progenitor cell survival.

Place, publisher, year, edition, pages
2008. Vol. 39, no 1, 32-9 p.
Keyword [en]
neural stem cell, neural progenitor, apoptosis, CNS development, cerebellum, Purkinje cells
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-100051DOI: 10.1016/j.mcn.2008.05.013ISI: 000259052500004PubMedID: 18619852OAI: oai:DiVA.org:uu-100051DiVA: diva2:209312
Available from: 2009-03-24 Created: 2009-03-24 Last updated: 2014-10-03Bibliographically approved
In thesis
1. Neural Stem and Progenitor Cells: Cellular Responses to Known and Novel Factors
Open this publication in new window or tab >>Neural Stem and Progenitor Cells: Cellular Responses to Known and Novel Factors
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neural stem cell self-renewal and differentiation are tightly regulated events during CNS development, leading to cell division into new neural stem cells or the formation of neurons and glial cells. This thesis focuses on the cellular responses induced by known and novel factors in neural stem and progenitor cells (NSPCs).

Platelet-derived growth factor (PDGF) signaling has previously been implicated in NSPC regulation as well as in tumor formation. In order to evaluate the differentiation process and find new regulators of NSPCs a micro-array screen was performed, evaluating transcription during normal differentiation and the effect of PDGF-AA in this process. The transcriptional profile of PDGF-AA treated NSPCs was shown to be an intermediate between the profiles of neural stem cells and their progeny. The NSPC transcriptome was also found to have similarities with that of experimental glioma. A previously non-characterized transcript, the nuclear receptor binding protein 2 (NRBP2), was identified and found to be expressed in the developing and adult mouse brain and in medulloblastoma. NRBP2 down-regulation rendered neural progenitors sensitive to induced cell death.

Different PDGF ligands interact with different combinations of PDGF receptors. Therefore NSPCs were stimulated with either PDGF-AA or -BB to further evaluate cellular responses with regard to the two specific isoforms. A divergent effect between the two isoforms in long-term proliferation and cell survival was found, with PDGF-BB being the most efficient stimulator.

Stem cell factor (SCF) has previously been identified as a regulator in the hematopoietic system and we showed that SCF induces a migratory response in NSPCs. In addition, SCF positively affected cell survival but had no effect on NSPC differentiation. Insights into the regulatory mechanisms involved in neural stem cell signaling are needed to develop diagnostic tools and novel treatments.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 63 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 504
Keyword
neural stem cell, differentiation, proliferation, migration, PDGF, SCF, NRBP2, medulloblastoma
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Biochemistry
Identifiers
urn:nbn:se:uu:diva-110722 (URN)978-91-554-7671-7 (ISBN)
Public defence
2010-01-15, B21, (BMC) Biomedical Center, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-12-21 Created: 2009-11-23 Last updated: 2014-10-23Bibliographically approved

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Forsberg-Nilsson, Karin

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