TY  - JOUR
AU  - Vastagh, Csaba
AU  - Schwirtlich, Marija
AU  - Kwakowsky, Andrea
AU  - Erdelyi, Ferenc
AU  - Margolis, Frank L.
AU  - Yanagawa, Yuchio
AU  - Katarova, Zoya
AU  - Szabo, Gabor
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/898
AB  - Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools.
PB  - Wiley, Hoboken
T2  - Developmental Neurobiology
T1  - The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons
EP  - 270
IS  - 3
SP  - 249
VL  - 75
DO  - 10.1002/dneu.22222
ER  - 

@article{
author = "Vastagh, Csaba and Schwirtlich, Marija and Kwakowsky, Andrea and Erdelyi, Ferenc and Margolis, Frank L. and Yanagawa, Yuchio and Katarova, Zoya and Szabo, Gabor",
year = "2015",
abstract = "Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools.",
publisher = "Wiley, Hoboken",
journal = "Developmental Neurobiology",
title = "The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons",
pages = "270-249",
number = "3",
volume = "75",
doi = "10.1002/dneu.22222"
}

Vastagh, C., Schwirtlich, M., Kwakowsky, A., Erdelyi, F., Margolis, F. L., Yanagawa, Y., Katarova, Z.,& Szabo, G.. (2015). The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons. in Developmental Neurobiology
Wiley, Hoboken., 75(3), 249-270.
https://doi.org/10.1002/dneu.22222

Vastagh C, Schwirtlich M, Kwakowsky A, Erdelyi F, Margolis FL, Yanagawa Y, Katarova Z, Szabo G. The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons. in Developmental Neurobiology. 2015;75(3):249-270.
doi:10.1002/dneu.22222 .

Vastagh, Csaba, Schwirtlich, Marija, Kwakowsky, Andrea, Erdelyi, Ferenc, Margolis, Frank L., Yanagawa, Yuchio, Katarova, Zoya, Szabo, Gabor, "The Spatiotemporal Segregation of GAD Forms Defines Distinct GABA Signaling Functions in the Developing Mouse Olfactory System and Provides Novel Insights into the Origin and Migration of GnRH Neurons" in Developmental Neurobiology, 75, no. 3 (2015):249-270,
https://doi.org/10.1002/dneu.22222 . .