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          Institute: MPI für experimentelle Medizin     Collection: Neurogenetics     Display Documents



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ID: 292205.0, MPI für experimentelle Medizin / Neurogenetics
The role of neuregulin-ErbB4 interactions on the proliferation and organization of cells in the subventricular zone
Authors:Ghashghaei, H. T.; Weber, Janet; Pevny, Larysa; Schmid, Ralf; Schwab, Markus H.; Lloyd, K. C. Kent; Eisenstat, David D.; Lai, Cary; Anton, E. S.
Language:English
Date of Publication (YYYY-MM-DD):2006-02
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbrev.:PNAS
Volume:103
Issue / Number:6
Start Page:1930
End Page:1935
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Coordinated regulation of neuronal progenitor differentiation in the subventricular zone (SVZ) is a fundamental feature of adult neurogenesis. However, the molecular control of this process remains mostly undeciphered. Here, we investigate the role of neuregulins (NRGs) in this process and show that a NRG receptor, ErbB4, is primarily expressed by polysialylated neural cell adhesion molecule immature neuroblasts but is also detected in a subset of GFAP(+) astroglial cells, ependymal cells, and DIx2(+) precursors in the SVZ. Of the NRG ligands, both NRG1 and -2 are expressed by immature polysialylated neural cell adhesion molecule neuroblasts in the SVZ. NRG2 is also expressed by some of the GFAP(+) putative stem cells lining the ventricles. infusion of exogenous NRG1 leads to rapid aggregation of DIx2(+) cells in the SVZ and affects the initiation and maintenance of organized neuroblast migration from the SVZ toward the olfactory bulb. In contrast, the infusion of NRG2 increased the number of Sox2 and GFAP(+) precursors in the SVZ. An outcome of this NRG2 effect is an increase in the number of newly generated migrating neuroblasts in the rostral migratory stream and GABAergic interneurons in the olfactory bulb. The analysis of conditional null mice that lack NRG receptor, ErbB4, in the nervous system revealed that the observed activities of NRG2 require ErbB4 activation. These results indicate that different NRG ligands affect distinct populations of differentiating neural precursors in the neurogenic regions of the mature forebrain. Furthermore, these studies identify NRG2 as a factor capable of promoting SVZ proliferation, leading to the formation of new neurons in vivo.
Free Keywords:adult neurogenesis; rostral migratory stream; schizophrenia ADULT MAMMALIAN BRAIN; NEURAL STEM-CELLS; GROWTH-FACTOR; HIPPOCAMPAL NEUROGENESIS; GABAERGIC INTERNEURONS; GENE-EXPRESSION; OLFACTORY-BULB; RECEPTOR; NEURONS; DIFFERENTIATION
External Publication Status:published
Document Type:Article
Communicated by:Klaus-Armin Nave
Affiliations:MPI für experimentelle Medizin/Neurogenetics
Relations:Has References-DOI:10.1073/pnas.0510410103
Identifiers:ISSN:0027-8424 [ID No:1]
ISI:000235311300048 [ID No:2]
ISI:000235311300048 [ID No:3]
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