The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain - PubMed (original) (raw)

Review

Alma Y Galvez-Contreras et al. Front Cell Neurosci. 2013.

Abstract

IN THE ADULT BRAIN, MULTIPOTENT PROGENITOR CELLS HAVE BEEN IDENTIFIED IN THREE AREAS: the ventricular-subventricular zone (VZ-SVZ), adjacent to the striatal wall of the lateral ventricles, the subgranular zone (SGZ), located at the dentate gyrus of the hippocampus and the subcallosal zone (SCZ), located between the corpus callosum and the CA1 and CA2 regions of the hippocampus. The neural progenitor cells of these regions express the epidermal growth factor receptor (EGFR, ErbB-1 or HER1). EGF, the most important ligand for the EGFR, is a potent mitogenic agent that stimulates proliferation, survival, migration and differentiation into the oligodendrocyte lineage. Other ErbB receptors also activate several intracellular pathways for oligodendrocyte specification, migration and survival. However, the specific downstream pathways related to oligodendrogenesis and the hierarchic interaction among intracellular signaling cascades is not well-known. We summarize the current data regarding the role of EGFR and ErbB family signaling on neural stem cells and the downstream cascades involved in oligodendrogenesis in the neurogenic niches of the adult brain. Understanding the mechanisms that regulate proliferation, differentiation, migration of oligodendrocytes and myelination is of critical importance for the field of neurobiology and constitutes a crucial step in the design of stem-cell-based therapies for demyelinating diseases.

Keywords: NG2 glia; epidermal growth factor; myelin; neural stem cell; oligodendrocyte; platelet-derived growth factor.

PubMed Disclaimer

Figures

Figure 1

Figure 1

The adult ventricular-subventricular zone (VZ-SVZ). 3-D reconstruction of this niche of neural stem cells located within the lateral wall of the lateral ventricles. Multiciliated ependymal cells, also called E2 cells, form pinwheel-like structures (in peach color) around the apical processes of type B1 cells (in blue). Biciliated ependymal cells as referred to E1 cells (in yellow). Type-C cells (in green) and type-A cells (in red). Type-B1 progenitors are neural stem cells that generate secondary progenitors (type-C cells), which in turn give rise to migrating neuroblast (type-A cells). Additionally, type-B1 cells generate oligodendrocyte progenitors in vivo. Both type-B and type-C progenitors express the EGFR. Note that type-B neural stem cells are in close contact with the cerebrospinal fluid and the adjacent blood vessels (BV).

Figure 2

Figure 2

The subgranular zone (SGZ) in the dentate gyrus of the adult hippocampus. Type-B1 cells (in blue) also known as type-1 cells or type-rA cells (radial astrocytes) are the neuronal progenitor cells in this region. Type-rA cells divide and produce type-D cells as referred to type-2 cells. Hippocampal neuroblasts migrate locally and incorporate into the granular layer where they differentiate in mature granular neurons (type-G cells). Type-B1 cells express EGFR and behave as putative neural stem cells in vitro.

Figure 3

Figure 3

The subcallosal zone (SCZ) is located between the hippocampus and the corpus callosum. The SCZ is a caudal extension of the VZ-SVZ that is no longer associated to the ventricular system. Type-B cells (in blue) generate type-C cells that, in turn, give rise to oligodendrocyte precursors (also called SCZ type-A cells) that migrate into the neighboring corpus callosum. Type-B and type-C cells isolated from the SCZ and cultured as neurospheres behave as neural stem cells in vitro. However, the cell type that expresses in vivo the ErbB family receptors is unknown.

Figure 4

Figure 4

The ErbB family receptors and their main cell signaling pathways: the Ras/MAPK, the PI3K/AKT and the PLCy pathways.

Figure 5

Figure 5

Biological effects reported in ErbB family proteins. The homo or heterodimerization of the ErbB proteins may generate similar effects. Homodimerization between EGFR/EGFR can originates proliferation MAPK activation and the heterodimeriizations of EGFR/ErbB2 undifferentiated state and enhanced mitogenic activity; EGFR/ErbB3 oligodendroglial cell fate via AKT and EGFR/ErbB4 neuronal and survival cell fate.

Figure 6

Figure 6

Hypothetical model of oligodendrocyte cell signaling, via EGFR and ErbB3 in adult neural stem and progenitors cells. Homodimerization between these two ErbB members could activate the PI3K or the STAT pathways that in turn can activate AKT and induces the expression of Olig-2, which in turn may determine oligodendroglial lineage.

Similar articles

Cited by

References

    1. Abe Y., Namba H., Zheng Y., Nawa H. (2009). In situ hybridization reveals developmental regulation of ErbB1-4 mRNA expression in mouse midbrain: implication of ErbB receptors for dopaminergic neurons. Neuroscience 161, 95–110 10.1016/j.neuroscience.2009.03.022 - DOI - PubMed
    1. Abrous D. N., Koehl M., Le Moal M. (2005). Adult neurogenesis: from precursors to network and physiology. Physiol. Rev. 85, 523–569 10.1152/physrev.00055.2003 - DOI - PubMed
    1. Adam Y., Mizrahi A. (2010). Circuit formation and maintenance–perspectives from the mammalian olfactory bulb. Curr. Opin. Neurobiol. 20, 134–140 10.1016/j.conb.2009.11.001 - DOI - PubMed
    1. Aguirre A., Dupree J. L., Mangin J. M., Gallo V. (2007). A functional role for EGFR signaling in myelination and remyelination. Nat. Neurosci. 10, 990–1002 10.1038/nn1938 - DOI - PubMed
    1. Aguirre A., Rubio M. E., Gallo V. (2010). Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature 467, 323–327 10.1038/nature09347 - DOI - PMC - PubMed

Publication types

LinkOut - more resources