Abstract During brain ontogenesis, the temporal and spatial generation of the different types of neuronal and glial cells from precursors occurs as a sequence of suc- cessive progenitor stages whose proliferation, survival and cell-fate choice are controlled by environmental and cellular regulatory molecules. Neurotransmitters belong to the chemical microenvironment of neural cells, even at the earliest stages of brain development. It is now es- tablished that specific neurotransmitter receptors are present on progenitor cells of the developing central ner- vous system and could play, during neural development, a role that has remained unsuspected until recently. The present review focuses on the occurrence of neurotrans- mitters and their corresponding ligand-gated ion channel receptors in immature cells, including neural stem cells of specific embryonic and neonatal brain regions. We summarize in vitro and in vivo data arguing that neuro- transmitters could regulate morphogenetic events such as proliferation, growth, migration, differentiation and sur- vival of neural precursor cells. The understanding of neurotransmitter function during early neural maturation could lead to the development of pharmacological tools aimed at improving adult brain repair strategies. Keywords Ligand-gated ion channels · Neural progenitors · Neurotransmitters · Proliferation · Migration · Differentiation · Survival Introduction Harmonious development of the mammalian central ner- vous system (CNS) during embryogenesis not only re- quires accurate course of genetic schedules but also de- pends on appropriate influences by various epigenetic signalling processes. In that respect, much effort has been recently devoted to characterize intrinsic and ex- trinsic factors regulating the behaviour of neural progen- itor cell populations during brain maturation. Recently, several secreted molecules such as growth factors, hor- mones and neurotransmitters have been implied in the extrinsic regulation of cell proliferation within the devel- oping telencephalon (reviewed by Cameron et al. 1998a). Among them, neurotransmitters are prominent candi- dates for transcellular signals that could influence the de- velopment of CNS cells, since they surround neural cells throughout the CNS maturation period (Cicirata et al. 1991; Miranda-Contreras et al. 1998, 1999, 2000) and since functional ligand-gated ionic channel receptors have been described in neural progenitors before the establishment of cortical and subcortical synapses (Belachew et al. 1998a; Flint et al. 1998; Haydar et al. 2000; Ma et al. 1998, 2000; Maric et al. 2000; Sah et al. 1997). Furthermore, several studies strongly suggest that neurotransmitters could behave as growth regulators dur- ing specific developmental periods (Antonopoulos et al. 1997; Brezun and Daszuta 2000; Butler et al. 1999; Cameron et al. 1998a; Fiszman et al. 1999; Haydar et al. 2000; Lauder et al. 1998; LoTurco et al. 1995; Ma et al. 1998, 2000; Wang et al. 1996; Weiss et al. 1998). Our present view of the CNS has changed dramatical- ly over the past few years. It is now well established that self-renewing neural stem and progenitor cells (Fig. 1) do persist in the adult mammalian brain and spinal cord This work was supported by the Fonds pour la Formation à la Re- cherche dans l’Industrie et dans l’Agriculture, the Fonds National de la Recherche Scientifique (FNRS), the Fondation Médicale Reine Elisabeth (FMRE), the Fondation Charcot and the Ligue Belge de la Sclérose en Plaques L. Nguyen ( ✉ ) · J.-M. Rigo · V. Rocher · S. Belachew B. Malgrange · B. Rogister · P. Leprince · G. Moonen Center for Cellular and Molecular Neurobiology, University of Liège, 17 Place Delcour, 4020 Liège, Belgium e-mail: Laurent.Nguyen@student.ulg.ac.be Tel.: +32-4-3665918, Fax: +32-4-3665912 S. Belachew · B. Rogister · G. Moonen Department of Neurology, University of Liège, C.H.U. (B35) Sart Tilman, 4000 Liège, Belgium Cell Tissue Res (2001) 305:187–202 DOI 10.1007/s004410000343 REVIEW Laurent Nguyen · Jean-Michel Rigo Véronique Rocher · Shibeshih Belachew Brigitte Malgrange · Bernard Rogister Pierre Leprince · Gustave Moonen Neurotransmitters as early signals for central nervous system development Received: 10 November 2000 / Accepted: 6 December 2000 / Published online: 20 February 2001 © Springer-Verlag 2001