Neurotransmitters as early signals for central nervous system development

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 successive 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 established that specific neurotransmitter receptors are present on progenitor cells of the developing central nervous system and could play, during neural development, a role that has remained unsuspected until recently. The present review focuses on the occurrence of neurotransmitters 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 neurotransmitters could regulate morphogenetic events such as proliferation, growth, migration, differentiation and survival 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.

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

“…Data from several groups have suggested that neural stem cells and neural progenitors may express low levels of the NMDA receptor [25,26]. We tested the expression of all known NMDAR subunits in wt ST14A cells by RT-PCR.…”

Autocrine/Paracrine Activation of the GABAAReceptor Inhibits the Proliferation of Neurogenic Polysialylated Neural Cell Adhesion Molecule-Positive (PSA-NCAM+) Precursor Cells from Postnatal Striatum

“…In addition to growth factors, hormones, integrins, and extracellular matrix components, neurotransmitters are present in the developing brain well before the onset of synaptic activity and have been shown to be part of the extrinsic control of CNS neurogenesis involving progenitor cell proliferation, migration, and differentiation as well as cell death (for review see Lauder, 1993;Cameron et al, 1998;Herlenius and Lagercrantz, 2001;Nguyen et al, 2001). Recent studies reported that functional neurotransmitter receptors are expressed by a wide variety of neuronal progenitors during embryonic development, thus pointing to a possible role in the transduction of important developmental cues (LoTurco et al, 1995;Flint et al, 1998;Haydar et al, 2000;Maric et al, 2000).…”

“…Considering that PSA-NCAM ϩ cells can be neatly used for brain repair purposes (Keirstead et al, 1999;Vitry et al, 2001), there is much interest in studying signaling factors that regulate their development. In this regard, it has been known for many years that neurotransmitters, which belong to the microenvironment of neural cells in vivo, regulate morphogenetic events preceding synaptogenesis such as cell proliferation, migration, differentiation, and death (for review, see Nguyen et al, 2001). Along this line, previous reports have suggested that GABA, the major inhibitory neurotransmitter in the mammalian brain, exerts trophic roles during CNS embryonic and postnatal development .…”

Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptors

“…There is increasing evidence that neurotransmitter signaling may be involved in early developmental events, some of which occur prior to synapse formation (Nguyen et al, 2001;Owens and Kriegstein, 2002). Serotonin (5-HT) is involved in early embryogenesis, even before neurons appear (Loric et al, 1995;Walther and Bader, 1999).…”

“…Serotonin interacts with seven families of receptors with different and sometimes opposing functions in a variety of cellular and developmental processes (Mouillet-Richard et al, 2000;Branchereau et al, 2002;Rumajogee et al, 2004). It is known that 5-HT receptors are functional and capable of playing a role in neuronal development from very early stages of ontogenesis (Walther and Bader, 1999;Nguyen et al, 2001), although little is known about the receptors and mechanisms involved. Furthermore, the developmental actions of serotonin may not only be initiated through binding to a cell surface receptor but also through the regulation of intracellular 5-HT via serotonin transporter activity (Fanburg and Lee, 1997;Rumajogee et al, 2004).…”