Short communication Developmental expression of glial fibrillary acidic protein mRNA in mouse forebrain germinal zones—implications for stem cell biology Irina J. Fox a,b , Andres A. Paucar b,c , Ichiro Nakano b,c , Jack Mottahedeh b,c , Joseph D. Dougherty b,d , Harley I. Kornblum b,c,e,f, * a UCLA Interdepartmental Program in Molecular, Cellular, and Integrative Physiology, David Geffen School of Medicine, Los Angeles, CA 90095, USA b UCLA Neural Stem Cell Research Center, David Geffen School of Medicine, Los Angeles, CA 90095, USA c Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA 90095, USA d UCLA Interdepartmental Program in the Neurosciences, David Geffen School of Medicine, Los Angeles, CA 90095, USA e Department of Pediatrics, David Geffen School of Medicine, Los Angeles, CA 90095, USA f UCLA Department of Energy Center for Molecular Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, USA Accepted 26 July 2004 Available online 2 September 2004 Abstract Postnatal neural stem cells (NSCs) express the btraditionalQ astrocyte marker, glial fibrillary acidic protein (GFAP). Here, we analyze the ontogeny of GFAP mRNA in mouse forebrain germinal zones (GZ). On embryonic day 15, mRNA distribution is highly restricted. Subsequently, expression expands to include many cells in the GZ regions adjacent to the cortex and septum but not to the striatum. Double immunostaining for GFAP and nestin did not demonstrate extensive overlap in the GZ of adult rats, suggesting that either few of the GFAP- expressing cells are stem cells, or that nestin is not a reliable marker for stem cells in the adult rat brain. The current findings indicate that while some GFAP-expressing cells in the GZ may be NSCs, most are not likely to function in a neurogenic capacity. D 2004 Elsevier B.V. All rights reserved. Theme: Development and generation Topic: Cell lineage and determination Keywords: Neural stem cell; Astrocyte; Progenitor; In situ hybridization; Quantitative RT-PCR; Subventricular zone Neural stem cells (NSCs) are capable of self-renewal and ultimate differentiation into neurons, astrocytes, and oligo- dendrocytes [6,31,35]. NSCs are found within the germinal zones (GZ) surrounding the lateral ventricles of both developing and adult brains [2,34]. Previous reports have demonstrated that postnatal NSCs express the intermediate filament, glial fibrillary acidic protein (GFAP). Tradition- ally, GFAP expression has been linked to astrocytes [18,23,25,33] serving to stabilize astrocyte cytoskeleton and maintain cell shape [12,36]. However, recent studies demonstrated that astrocyte monolayers are capable of forming NSC-containing neurospheres in vitro [20] and that GFAP-positive type B cells in adult subependyma (a GZ persisting into adulthood) are NSCs [9]. Furthermore, eradication of GFAP-positive cells in vivo or in vitro prevented the proliferation of multipotent progenitors from the GZ of GFAP thymidine kinase (TK) transgenic mice at postnatal ages [14,28]. Despite ample evidence that post- natal NSCs express GFAP, little is known about their ontogeny. Previous studies of the ontogeny of GFAP expression have largely focused on the production of astrocytes [4,5,17,18,27,29,30,33]. In the current study, we have specifically examined the ontogeny of GFAP expres- sion in developing GZ in order to determine the location and timing of appearance of GFAP-expressing progenitors. 0165-3806/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.devbrainres.2004.07.011 * Corresponding author. UCLA School of Medicine, Room 1126 CIMI, 700 Westwood Plaza, Los Angeles, CA 90095, USA. Tel.: +1 310 794 7866; fax: +1 310 206 8975. E-mail address: hkornblum@mednet.ucla.edu (H.I. Kornblum). Developmental Brain Research 153 (2004) 121 – 125 www.elsevier.com/locate/devbrainres