GABA signalling during development: new data and old questions

Abstract. In addition to being the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA) is thought to play a morphogenetic role in embryonic development. During the last decade, considerable progress has been made in elucidating the molecular mechanisms involved in GABA synthesis and biological action. The present review is an attempt to summarise recent results on the ontogeny of the different components of embryonic GABA signalling with an emphasis on the synthesis of GABA by different molecular forms of glutamic acid decarboxylase (GAD).

[1]  S. Tobet,et al.  Effects of γ-Aminobutyric AcidA Receptor Manipulation on Migrating Gonadotropin-Releasing Hormone Neurons through the Entire Migratory Route in Vivo and in Vitro. , 2000, Endocrinology.

[2]  M. Seike,et al.  The reeler gene-associated antigen on cajal-retzius neurons is a crucial molecule for laminar organization of cortical neurons , 1995, Neuron.

[3]  N. Nelson,et al.  Molecular characterization of four pharmacologically distinct gamma-aminobutyric acid transporters in mouse brain [corrected]. , 1993, The Journal of biological chemistry.

[4]  S. Anderson,et al.  Mutations of the Homeobox Genes Dlx-1 and Dlx-2 Disrupt the Striatal Subventricular Zone and Differentiation of Late Born Striatal Neurons , 1997, Neuron.

[5]  D. Reichling,et al.  Mechanisms of GABA and glycine depolarization‐induced calcium transients in rat dorsal horn neurons. , 1994, The Journal of physiology.

[6]  J. Lauder,et al.  Neurotransmitters as growth regulatory signals: role of receptors and second messengers , 1993, Trends in Neurosciences.

[7]  J. A. Payne,et al.  The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation , 1999, Nature.

[8]  J. Barker,et al.  Differential Response of Cortical Plate and Ventricular Zone Cells to GABA as a Migration Stimulus , 1998, The Journal of Neuroscience.

[9]  S. Tobet,et al.  Effects of gamma-aminobutyric acid(A) receptor manipulation on migrating gonadotropin-releasing hormone neurons through the entire migratory route in vivo and in vitro. , 2000, Endocrinology.

[10]  J. Barker,et al.  Complementary expressions of transcripts encoding GAD67 and GABAA receptor alpha 4, beta 1, and gamma 1 subunits in the proliferative zone of the embryonic rat central nervous system , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  A. Pol,et al.  GABA release from mouse axonal growth cones , 2000, The Journal of physiology.

[12]  D. L. Martin,et al.  Two isoforms of glutamate decarboxylase: why? , 1998, Trends in pharmacological sciences.

[13]  E. Floor,et al.  Association of l-Glutamic Acid Decarboxylase to the 70-kDa Heat Shock Protein as a Potential Anchoring Mechanism to Synaptic Vesicles* , 2000, The Journal of Biological Chemistry.

[14]  D. L. Martin,et al.  Regulation of gamma-aminobutyric acid synthesis in the brain. , 1993, Journal of neurochemistry.

[15]  R. Greenspan,et al.  Distinct protein forms are produced from alternatively spliced bicistronic glutamic acid decarboxylase mRNAs during development , 1994, Molecular and cellular biology.

[16]  J. Taylor,et al.  GABAergic Growth Cones: Release of Endogenous γ‐Aminobutyric Acid Precedes the Expression of Synaptic Vesicle Antigens , 1990, Journal of neurochemistry.

[17]  J. Barker,et al.  GABA receptor antagonists modulate postmitotic cell migration in slice cultures of embryonic rat cortex. , 2000, Cerebral cortex.

[18]  C. Houser,et al.  Two Forms of the γ‐Aminobutyric Acid Synthetic Enzyme Glutamate Decarboxylase Have Distinct Intraneuronal Distributions and Cofactor Interactions , 1991, Journal of neurochemistry.

[19]  H. Supèr,et al.  Disruption of neuronal migration and radial glia in the developing cerebral cortex following ablation of Cajal-Retzius cells. , 2000, Cerebral cortex.

[20]  J. Barker,et al.  Anatomical Gradients in Proliferation and Differentiation of Embryonic Rat CNS Accessed by Buoyant Density Fractionation: α3, β3 and γ2 GABAA Receptor Subunit Co‐expression by Post‐mitotic Neocortical Neurons Correlates Directly with Cell Buoyancy , 1997, The European journal of neuroscience.

[21]  P. Gordon-Weeks,et al.  Calcium‐Independent γ‐Aminobutyric Acid Release from Growth Cones: Role of γ‐Aminobutyric Acid Transport , 1991 .

[22]  W Wisden,et al.  The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  N. Brecha,et al.  GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  S. Anderson,et al.  Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. , 1999, Cerebral cortex.

[25]  A. Schousboe,et al.  Neurotransmitters as developmental signals , 1991, Neurochemistry International.

[26]  K. Obata,et al.  Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65 , 2000, Brain Research.

[27]  J. Barker,et al.  Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development. , 1993, Brain research. Developmental brain research.

[28]  P. Rakić,et al.  Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  J. Altman,et al.  The development of the rat spinal cord. , 1984, Advances in anatomy, embryology, and cell biology.

[30]  A. Kriegstein,et al.  GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis , 1995, Neuron.

[31]  T. Yagi,et al.  Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[32]  K. Obata,et al.  GABA and histogenesis in fetal and neonatal mouse brain lacking both the isoforms of glutamic acid decarboxylase , 1999, Neuroscience Research.

[33]  A. Kriegstein,et al.  Excitatory GABA Responses in Embryonic and Neonatal Cortical Slices Demonstrated by Gramicidin Perforated-Patch Recordings and Calcium Imaging , 1996, The Journal of Neuroscience.

[34]  S. Baekkeskov,et al.  Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble. , 1991, The Journal of biological chemistry.

[35]  P. Rakic,et al.  Differential Modulation of Proliferation in the Neocortical Ventricular and Subventricular Zones , 2000, The Journal of Neuroscience.

[36]  E. Mugnaini,et al.  Domain‐restricted expression of two glutamic acid decarboxylase genes in midgestation mouse embryos , 2000, The Journal of comparative neurology.

[37]  J. D. del Río,et al.  Developmental history of the subplate and developing white matter in the murine neocortex. Neuronal organization and relationship with the main afferent systems at embryonic and perinatal stages. , 2000, Cerebral cortex.

[38]  Qing-Rong Liu,et al.  Molecular Characterization of Four Pharmacologically Distinct a-Aminobutyric Acid Transporters in Mouse Brain * , 2001 .

[39]  M. Blaustein,et al.  GABA efflux from synaptosomes: Effects of membrane potential, and external GABA and cations , 2005, The Journal of Membrane Biology.

[40]  A. Schousboe,et al.  Effect of Repeated Treatment with a γ‐Aminobutyric Acid Receptor Agonist on Postnatal Neural Development in Rats , 1987, Journal of neurochemistry.

[41]  S. B. Kater,et al.  Neurotransmitter regulation of neuronal outgrowth, plasticity and survival , 1989, Trends in Neurosciences.

[42]  Modulation of the truncated GAD25 by estrogen in the olfactory bulb of adult rats , 2000, Neuroreport.

[43]  T. Südhof,et al.  Synaptic assembly of the brain in the absence of neurotransmitter secretion. , 2000, Science.

[44]  S. Kash,et al.  The Hydrophilic Isoform of Glutamate Decarboxylase, GAD67, Is Targeted to Membranes and Nerve Terminals Independent of Dimerization with the Hydrophobic Membrane-anchored Isoform, GAD65* , 1999, The Journal of Biological Chemistry.

[45]  A. Schousboe,et al.  The GABA Paradox , 1999, Journal of neurochemistry.

[46]  A. Rotter,et al.  Embryonic and postnatal expression of four gamma‐aminobutyric acid transporter mRNAs in the mouse brain and leptomeninges , 1996, The Journal of comparative neurology.

[47]  L. Medina-Kauwe,et al.  gamma-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. , 1995, Comparative biochemistry and physiology. Part A, Physiology.

[48]  David L. Martin,et al.  Structural features and regulatory properties of the brain glutamate decarboxylases , 2000, Neurochemistry International.

[49]  S. Baekkeskov,et al.  Membrane anchoring of the autoantigen GAD65 to microvesicles in pancreatic beta-cells by palmitoylation in the NH2-terminal domain , 1992, The Journal of cell biology.

[50]  T. Gómez,et al.  Characterization of spontaneous calcium transients in nerve growth cones and their effect on growth cone migration , 1995, Neuron.

[51]  A. Schousboe,et al.  Temporal development of gaba agonist induced alterations in ultrastructure and gaba receptor expression in cultured cerebellar granule cells , 1987, International Journal of Developmental Neuroscience.

[52]  N. Brecha,et al.  GAT-3, a High-Affinity GABA Plasma Membrane Transporter, Is Localized to Astrocytic Processes, and It Is Not Confined to the Vicinity of GABAergic Synapses in the Cerebral Cortex , 1996, The Journal of Neuroscience.

[53]  Nicholas C. Spitzer,et al.  In vivo regulation of axon extension and pathfinding by growth-cone calcium transients , 1999, Nature.

[54]  S. Baekkeskov,et al.  Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45 are required for membrane anchoring of glutamic acid decarboxylase, GAD65 , 1994, The Journal of cell biology.

[55]  J. Rubenstein,et al.  Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. , 1995, Genes & development.

[56]  J. Barker,et al.  Initially expressed early rat embryonic GABAA receptor Cl– ion channels exhibit heterogeneous channel properties , 1998, The European journal of neuroscience.

[57]  P. Spoerri Neurotrophic effects of GABA in cultures of embryonic chick brain and retina , 1988, Synapse.

[58]  J. Barker,et al.  Ontogeny of GABAA receptor subunit mRNAs in rat spinal cord and dorsal root ganglia , 1993, The Journal of comparative neurology.

[59]  H. Mitoma,et al.  Synaptic localization of the 67,000 mol. wt isoform of glutamate decarboxylase and transmitter function of GABA in the mouse cerebellum lacking the 65,000 mol. wt isoform , 1999, Neuroscience.

[60]  P. Gordon-Weeks,et al.  Developmental Changes in the Calcium Dependency of γ‐Aminobutyric Acid Release from Isolated Growth Cones: Correlation with Growth Cone Morphology , 1989, Journal of neurochemistry.

[61]  J. Barker,et al.  GABAergic cells and signals in CNS development. , 1998, Perspectives on developmental neurobiology.

[62]  I. Priede,et al.  Multiplicity of glutamic acid decarboxylases (GAD) in vertebrates: molecular phylogeny and evidence for a new GAD paralog. , 1999, Molecular biology and evolution.

[63]  D. Gottlieb,et al.  Developmentally regulated expression of an exon containing a stop codon in the gene for glutamic acid decarboxylase. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[64]  N. Saunders,et al.  Synaptogenesis in the neocortical anlage and early developing neocortex of rat embryos. , 1996, Acta anatomica.

[65]  S. Chessler,et al.  Alternative Splicing of GAD67 Results in the Synthesis of a Third Form of Glutamic-acid Decarboxylase in Human Islets and Other Non-neural Tissues* , 2000, The Journal of Biological Chemistry.

[66]  D. Hanahan,et al.  Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[67]  M. Hatten,et al.  Embryonic cerebellar neurons accumulate [3H]-gamma-aminobutyric acid: visualization of developing gamma-aminobutyric acid-utilizing neurons in vitro and in vivo , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[68]  J. Wolff,et al.  γ‐Aminobutyric Acid Outside the Mammalian Brain , 1990 .

[69]  A. Schousboe,et al.  Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function. , 1998, Perspectives on developmental neurobiology.

[70]  K. Rimvall,et al.  Regulation of γ‐Aminobutyric Acid Synthesis in the Brain , 1993 .

[71]  O. Jørgensen,et al.  γ‐Aminobutyric Acid Affects the Developmental Expression of Neuron‐Associated Proteins in Cerebellar Granule Cell Cultures , 1986, Journal of neurochemistry.

[72]  J. Wolff,et al.  Fine structural changes in the superior cervical ganglion of adult rats after long-term administration of baclofen, a GABAB receptor agonist , 1990, Neuroscience.

[73]  J. Barker,et al.  Neuroepithelial cells in the rat spinal cord express glutamate decarboxylase immunoreactivity in vivo and in vitro , 1992, The Journal of comparative neurology.

[74]  S. Wray,et al.  GABA Inhibits Migration of Luteinizing Hormone-Releasing Hormone Neurons in Embryonic Olfactory Explants , 1998, The Journal of Neuroscience.

[75]  D. L. Martin,et al.  Heteromers of Glutamate Decarboxylase Isoforms Occur in Rat Cerebellum , 1996, Journal of neurochemistry.

[76]  J. Barker,et al.  GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[77]  A. Kriegstein,et al.  Changing properties of GABA(A) receptor-mediated signaling during early neocortical development. , 1999, Journal of neurophysiology.

[78]  R. Olsen,et al.  GABA Alters GABAA Receptor mRNAs and Increases Ligand Binding , 1993, Journal of neurochemistry.

[79]  J. Barker,et al.  Analysis of the anatomical distribution of GAD67 mRNA encoding truncated glutamic acid decarboxylase proteins in the embryonic rat brain. , 1994, Brain research. Developmental brain research.

[80]  T. Verdoorn,et al.  Prenatal ontogeny of the gabaergic system in the rat brain: An immunocytochemical study , 1986, Neuroscience.

[81]  J. Barker,et al.  Developmental kinetics of GAD family mRNAs parallel neurogenesis in the rat spinal cord , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[82]  C. Walsh,et al.  Reelin Binds α3β1 Integrin and Inhibits Neuronal Migration , 2000, Neuron.

[83]  F. Jursky,et al.  Developmental Expression of the GABA Transporter GAT4 , 1996 .

[84]  M. Capecchi,et al.  Cleft palate in mice with a targeted mutation in the gamma-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[85]  R. Somogyi,et al.  Differential regulation of adult and embryonic glutamate decarboxylases in rat dentate granule cells after kainate-induced limbic seizures , 2000, Neuroscience.

[86]  M. Erlander,et al.  Two genes encode distinct glutamate decarboxylases , 1991, Neuron.

[87]  Y. Ben-Ari,et al.  GABA: an excitatory transmitter in early postnatal life , 1991, Trends in Neurosciences.