A quantitative immunohistochemical study of macroglial cell development in the rat optic nerve: In vivo evidence for two distinct astrocyte lineages

Miller, Robert H.; David, Sam; Patel, Ramilla; Abney, Erika R.; Raff, Martin

doi:10.1016/0012-1606(85)90432-4

Cited by 310 publications

(155 citation statements)

References 17 publications

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“…Of these, 73 probe sets (representing 52 unique genes) were induced in vitro but expressed at levels similar to or lower than OPC levels in the acutely purified OLs, a pattern we would predict for genes specifically upregulated in the small percentage of type 2 astrocytes generated in our cultures that are not present among acutely purified OLs. Consistent with this, GFAP, which is expressed by 2As (Miller et al, 1985), and other well described astrocyte genes, shared this expression pattern. Therefore, these probable "2A" genes were excluded from additional analyses, leaving 880 probe sets (726 unique genes) identified as strongly regulated in differentiating OLs.…”

Section: Generation Of a Comprehensive Database Of Gene Expression Dusupporting

confidence: 75%

Functional Genomic Analysis of Oligodendrocyte Differentiation

Dugas¹,

Tai²,

Speed³

et al. 2006

J. Neurosci.

294

353

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To better understand the molecular mechanisms governing oligodendrocyte (OL) differentiation, we have used gene profiling to quantitatively analyze gene expression in synchronously differentiating OLs generated from pure oligodendrocyte precursor cells in vitro. By comparing gene expression in these OLs to OLs generated in vivo, we discovered that the program of OL differentiation can progress normally in the absence of heterologous cell-cell interactions. In addition, we found that OL differentiation was unexpectedly prolonged and occurred in at least two sequential stages, each characterized by changes in distinct complements of transcription factors and myelin proteins. By disrupting the normal dynamic expression patterns of transcription factors regulated during OL differentiation, we demonstrated that these sequential stages of gene expression can be independently controlled. We also uncovered several genes previously uncharacterized in OLs that encode transmembrane, secreted, and cytoskeletal proteins that are as highly upregulated as myelin genes during OL differentiation. Last, by comparing genomic loci associated with inherited increased risk of multiple sclerosis (MS) to genes regulated during OL differentiation, we identified several new positional candidate genes that may contribute to MS susceptibility. These findings reveal a previously unexpected complexity to OL differentiation and suggest that an intrinsic program governs successive phases of OL differentiation as these cells extend and align their processes, ensheathe, and ultimately myelinate axons.

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Section: Generation Of a Comprehensive Database Of Gene Expression Dusupporting

confidence: 75%

Functional Genomic Analysis of Oligodendrocyte Differentiation

Dugas¹,

Tai²,

Speed³

et al. 2006

J. Neurosci.

294

353

View full text Add to dashboard Cite

show abstract

“…GLT-1 in embryonic white matter may be in astroglia; however, in spinal cord white matter, GLT-1 enrichment preceded the enrichment of GFAP. GLT-1 may be localized in myelin sheaths of developing oligodendroglia that closely contact growing axons; however, oligodendrocytes first appear at P0 in rat optic nerve (Miller et al, 1985), although we found the optic tract enriched in GLT-1 at E18. Alternatively, although GLT-1 is primarily astroglial in adult rat brain (Rothstein et al, 1994;Chaudhry et al, 1995;Lehre et al, 1995), in fetal rat brain, GLT-1 protein may also be expressed in neurons at levels in the cell body that are below the limits of immunological detection, but at levels sufficient for detection in growing axons.…”

Section: Glt-1 Localization In White Matter During Late Embryogenesiscontrasting

confidence: 70%

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

Furuta¹,

1997

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Extracellular glutamate concentrations are regulated by glial and neuronal transporter proteins. Four glutamate transporter subtypes have been identified in rat brain; GLAST and GLT-1 are primarily astrocytic, whereas EAAC1 and EAAT4 are neuronal. Using immunoblotting and immunohistochemistry with subtype-specific antipeptide antibodies, we examined the protein expression and regional and cellular localization of each glutamate transporter subtype in embryonic and postnatal rat CNS. Each transporter had a specific pattern of expression. GLAST immunoreactivity was low prenatally but became enriched in cerebellar Bergmann glia early postnatally and then was also present in forebrain later postnatally. The posttranslational modification of GLAST was unique among the subtypes; glycosylated GLAST increased with maturation, whereas nonglycosylated protein decreased in abundance postnatally. GLT-1 was present in fetal brain and spinal cord, with expression progressively increasing to adult levels throughout the neuraxis by postnatal day 26. Transient expression of GLT-1 immunoreactivity along axonal pathways was observed prenatally, in contrast to the exclusive localization of GLT-1 to astrocytes in the adult CNS. EAAC1, localized to neurons, was enriched in forebrain, diencephalon, and hindbrain during prenatal and postnatal development. EAAC1 expression was greater in newborn brain compared with adult brain. EAAT4 had a region-specific distribution; EAAT4 was mainly in cerebellum, localized to Purkinje cells, with much lower levels in forebrain. EAAT4 levels increased in cerebellum with age. We conclude that during CNS development the expression of glutamate transporter subtypes is differentially regulated, regionally segregated, and coordinated.

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“…They migrate from the optic nerve head into the inner retina. Astrocytes first appear in the developing rat optic nerve at E (embryonic day) 16 and increase in number until 6 weeks after birth (Miller et al, 1985). They form a corona of processes around the optic nerve head at E18, cover approximately 35% of the retina at birth, and reach the periphery of the retina by P (postnatal day) 8 (Ling et al, 1989).…”

Section: Maumenee Personal Communication)mentioning

confidence: 99%

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Sinha

Klise

Sergeev

et al. 2008

Molecular and Cellular Neuroscience

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Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague-Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the βA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina.

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A quantitative immunohistochemical study of macroglial cell development in the rat optic nerve: In vivo evidence for two distinct astrocyte lineages

Cited by 310 publications

References 17 publications

Functional Genomic Analysis of Oligodendrocyte Differentiation

Functional Genomic Analysis of Oligodendrocyte Differentiation

Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

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