title: GLT1, glial glutamate transporter, is transiently expressed in neurons and develops astrocyte specificity only after midgestation in the ovine fetal brain.
abstract: Glutamate transport is a primary mechanism for regulating extracellular levels of glutamate in the central nervous system. GLT1, the most abundant of the known high-affinity glutamate transporters, is found exclusively in astrocytes in adult brain of several species, but we and others have recently identified neurons that transiently express GLT1 protein in the developing brain. We now demonstrate the development of cell type specificity for GLT1 expression at 60, 71, and 136 days' gestation in the developing sheep brain (term = 145 days). At 60 and 71 days of gestation, GLT1 colocalizes with calbindin in Purkinje cells in the cerebellum, and this expression pattern has a novel distribution that is reminiscent of the parasagittal zebrin-like bands. GLT1 immunoreactivity simultaneously occurs in periventricular white matter, anterior commissure, and striatal white matter, dissipating by 136 days. GLT1 protein expression within astrocytes is developmentally regulated, appearing first in vimentin positive radial glia at 60 and 71 days and then switching to GFAP positive parenchymal and perivascular astrocytes at 136 days. Expression of GLT1 in subsets of vimentin-positive astrocytes persists in white matter but not in cortex. These results identify a novel compartmentation within cerebellar cortex and neuronal and axonal pathway localization of GLT1, suggesting the participation of this glutamate transporter in the development of the topographic organization of cerebellar cortex and a transient neuronal function for GLT1 in developing brain. In addition, GLT1 expression is highly plastic, being neither exclusively astroglial nor uniformly expressed in different populations of astrocytes during brain development.
authors.affiliation: Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Northington
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
authors.forename: R C
authors.initials: RC
authors.lastname: Koehler
authors.forename: L J
authors.initials: LJ
authors.lastname: Martin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D027322:Amino Acid Transport System X-AG; D000818:Animals; D000918:Antibody Specificity; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D005333:Fetus / Q000737:chemistry; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000276:immunology; D018698:Glutamic Acid / Q000378:metabolism; D009412:Nerve Fibers / Q000737:chemistry / Q000378:metabolism; D011689:Purkinje Cells / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D012756:Sheep; D014746:Vimentin / Q000032:analysis / Q000276:immunology
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin; D018698:Glutamic Acid