Neuron Glia Biology

Research Article

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

Adan Aguirrea1 c1 and Vittorio Galloa1

a1 Center for Neuroscience Research, Children's National Medical Center, Washington, USA

Abstract

Neural progenitor cells that express the NG2 proteoglycan are present in different regions of the adult mammalian brain where they display distinct morphologies and proliferative rates. In the developing postnatal and adult mouse, NG2+ cells represent a major cell population of the subventricular zone (SVZ). NG2+ cells divide in the anterior and lateral region of the SVZ, and are stimulated to proliferate and migrate out of the SVZ by focal demyelination of the corpus callosum (CC). Many NG2+ cells are labeled by GFP-retrovirus injection into the adult SVZ, demonstrating that NG2+ cells actively proliferate under physiological conditions and after demyelination. Under normal physiological conditions and after focal demyelination, proliferation of NG2+ cells is significantly attenuated in wa2 mice, which are characterized by reduced signaling of the epidermal growth factor receptor (EGFR). This results in reduced SVZ-to-lesion migration of NG2+ cells and oligodendrogenesis in the lesion. Expression of vascular endothelial growth factor (VEGF) and EGFR ligands, such as heparin binding-EGF and transforming growth factor α, is upregulated in the SVZ after focal demyelination of the CC. EGF-induced oligodendrogenesis and myelin protein expression in wild-type SVZ cells in culture are significantly attenuated in wa2 SVZ cells. Our results demonstrate that the response of NG2+ cells in the SVZ and their subsequent differentiation in CC after focal demyelination depend on EGFR signaling.

(Received December 07 2007)

(Revised February 15 2008)

(Accepted February 22 2008)

Correspondence:

c1 Correspondence should be addressed to Drs Adan Aguirre And Vittorio Gallo, Center for Neuroscience Research, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA phone: +1 202-476 4996 fax: +1 202-476 884 4988 email: vgallo@cnmcresearch.org, aaguirre@cnmcresearch.org