Control of cell survival and proliferation of postnatal PSA-NCAM + progenitors Nathalie Gago, a,b, * Virginia Avellana-Adalid, c Anne Baron-Van Evercooren, c and Michael Schumacher a a INSERM U 488, 80, rue du Ge ´ne ´ral Leclerc, 94276 Bice ˆtre, France b Escuela de Medicina J.M. Vargas, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela c Laboratoire des Affections de la Mye ´line et des Canaux Ioniques Musculaires, INSERM U546, 75634 Paris Cedex 13, France Received 17 September 2001; revised 10 June 2002; accepted 5 August 2002 Abstract In the present work, we studied the effects of several growth factors on survival and proliferation of freshly isolated neural progenitors expressing the polysialylated form of neural cell adhesion molecule (PSA-NCAM). Cells were obtained from postnatal day 2 rat forebrain, using isolation method. We found that (1) insulin-like growth factor 1 (IGF-1) exerts a powerful survival effect by inhibiting apoptotic cell death, (2) epidermal growth factor (EGF) strongly increases cell proliferation, (3) the combination of IGF-1 plus EGF promotes cellular expansion, (4) basic fibroblast growth factor displays only a weak mitogenic effect, and (5) platelet-derived growth factor-AA (PDGF-AA) has no effect on cell survival and proliferation. These results suggest that the postnatal PSA-NCAM + progenitors characterized in the present work may represent a transitional stage, between the embryonic EGF-responsive neural progenitors and the postnatal PSA-NCAM + progenitors already described that are PDGF-responsive. For these “early PSA-NCAM + progenitors,” insulin-like growth factor 1 and EGF seem to play a pivotal role in the control of cell death and cell proliferation. © 2003 Elsevier Science (USA). All rights reserved. Introduction During brain development, the majority of cells (neu- rons, astrocytes, and oligodendrocytes) arise from two spe- cialized germinative zones, the ventricular zone (VZ) and the subventricular zone (SVZ). The different cell types spread from these germinative zones on a precise schedule. The VZ forms early in development, lines the lateral ven- tricles and gives rise to neurons and radial glia (Sidman et al., 1959). The SVZ emerges at later stages of development, adjacent to the VZ. During the late embryonic and early postnatal period when neurogenesis is almost complete, the SVZ actively generates glial cells (astrocytes and oligoden- drocytes) (Altman, 1969; Goldman, 1995). The oligodendrocyte-type 2 (O-2A) astrocyte is probably the most extensively studied glial progenitor and the earliest committed progenitor of the oligodendroglial lineage. This cell type was first isolated from neonatal optic nerve and can give rise in vitro either to oligodendrocytes or to type 2 astrocytes (Raff et al., 1983). However, evidence supports the view that O-2A astrocyte progenitors do not produce astrocytes in vivo, and they may thus be considered as an oligodendrocyte precursor (OP), exclusively committed to the oligodendroglial lineage (Espinosa de los Monteros et al., 1993; Franklin and Blakemore, 1995). These cells dis- play high proliferative and migratory capacities (for re- views, see Ludwin, 1997; Norton, 1996), show a character- istic bi- or tripolar morphology, express the ganglioside GD3 (Goldman et al., 1984), and are immunoreactive for the antibody A2B5 (Raff et al., 1983), which recognizes a mixture of gangliosides and sulfatides (Einsenbarth et al., 1979). These OPs differentiate progressively into mature oligodendrocytes, a process that is accompanied by the loss of their cell proliferation and motility. Mature oligodendro- * Corresponding author. Ca ´tedra de Fisiologı ´a, Escuela de Medicina J.M. Vargas, Facultad de Medicina, Universidad Central de Venezuela, Edificio de Ciencias Ba ´sicas II, Esquina San Lorenzo, San Jose ´, Caracas, Venezuela. Fax: +00582125628610. E-mail address: gagonat@hotmail.com (N. Gago). R Available online at www.sciencedirect.com Molecular and Cellular Neuroscience 22 (2003) 162–178 www.elsevier.com/locate/ymcne 1044-7431/03/$ – see front matter © 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S1044-7431(02)00030-1