Embryonic expression of myelin genes: Evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube

Yu, Weiping; Collarini, Ellen J.; Pringle, Nigel; Richardson, William D.

doi:10.1016/0896-6273(94)90450-2

Cited by 231 publications

(161 citation statements)

References 44 publications

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“…A similar profile of mRNA accumulation was also found for the mRNAs encoding MBP, PLP, and CNP1, the larger of the two CNP transcripts. The smaller CNP transcript, encoding the CNP2 isoform, is expressed much earlier in development, probably by oligodendrocyte precursors Yu et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

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Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

et al. 1997

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We have investigated the patterns of postnatal brain expression and DNA binding of Gtx, a homeodomain transcription factor. Gtx mRNA accumulates in parallel with the RNAs encoding the major structural proteins of myelin, myelin basic protein (MBP), and proteolipid protein (PLP) during postnatal brain development; Gtx mRNA decreases in parallel with MBP and PLP mRNAs in the brains of myelin-deficient rats, which have a point mutation in the PLP gene. Gtx mRNA is expressed in differentiated, postmitotic oligodendrocytes but is not found in oligodendrocyte precursors or astrocytes. These data thus demonstrate that Gtx is expressed uniquely in differentiated oligodendrocytes in postnatal rodent brain and that its expression is regulated in parallel with the major myelin protein mRNAs, encoding MBP and PLP, under a variety of physiologically relevant circumstances.Using a Gtx fusion protein produced in bacteria, we have confirmed that Gtx is a sequence-specific DNA-binding protein, which binds DNA sequences containing a core AT-rich homeodomain binding site. Immunoprecipitation of labeled DNA fragments encoding either the MBP or PLP promoter regions with this fusion protein has identified several Gtx-binding fragments, and we have confirmed these data using an electrophoretic mobility shift assay. In this way we have identified four Gtx binding sites within the first 750 bp of the MBP promoter and four Gtx binding sites within the first 1.3 kb of the PLP promoter. In addition, inspection of the PLP promoter sequence demonstrates the presence of six additional Gtx binding sites. These data, taken together, strongly suggest that Gtx is important for the function of differentiated oligodendrocytes and may be involved in the regulation of myelin-specific gene expression.

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Section: Resultsmentioning

confidence: 99%

“…Oligodendrocyte precursors migrate out from regions surrounding the developing ventricles (Yu et al, 1994) to populate developing axon tracts. Before the onset of myelination, these proliferating oligodendrocyte precursors stop dividing and begin to synthesize the major myelin structural proteins in an orderly sequence.…”

mentioning

confidence: 99%

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

et al. 1997

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“…In this study, we used the CNP promoter to drive Cre expression for generation of O-Arf6-CKO mice, as CNP is detectable in OPCs at E11.5 to E12 and its expression is maintained in mature oligodendrocytes 17 . However, although this promoter-Cre system achieves essentially 100% targeted gene ablation in oligodendrocytes, CNP-Cre-mediated recombination is not 100% efficient for OPCs 18 .…”

Section: Discussionmentioning

confidence: 99%

Trans-regulation of oligodendrocyte myelination by neurons through small GTPase Arf6-regulated secretion of fibroblast growth factor-2

et al. 2014

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The small G protein ADP-ribosylation factor 6 (Arf6) plays important roles in a wide variety of membrane dynamics-based cellular events such as neurite outgrowth and spine formation in vitro. However, little is known about physiological function of Arf6 in vivo. Here we generate conditional knockout mice lacking Arf6 in neurons, oligodendrocytes, or both cell lineages, and unexpectedly find that Arf6 expression in neurons, but not in oligodendrocytes, is crucial for oligodendrocyte myelination in the hippocampal fimbria and the corpus callosum during development, and that this is through the regulation of secretion of fibroblast growth factor-2, a guidance factor for migration of oligodendrocyte precursor cells (OPCs). These results suggest that Arf6 in neurons plays an important role in OPC migration through regulation of FGF-2 secretion during neuronal development.

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“…DM20 transcripts are detected in the blastocyst (Skoff et al, 2004), seminiferous tubules, myocardial cells, thymus, and spleen (Campagnoni et al, 1992;Pribyl et al, 1996). In the mouse nervous system, DM20 is expressed in neural progenitors as early as embryonic day 9.5 (E9.5) and in oligodendrocyte progenitors by E14.5 (Timsit et al, 1992(Timsit et al, , 1995Yu et al, 1994;Fanarraga et al, 1996;Dickinson et al, 1997;Spassky et al, 1998;Gudz et al, 2006). DM20 also accumulates in multiple glial cell types, including olfactory bulb ensheathing cells (OECs), spinal and autonomic ganglia satellite cells, Schwann cells, and enteric glia (Griffiths et al, 1989(Griffiths et al, , 1995Puckett et al, 1987;Dickinson et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

Tuason¹,

Rastikerdar²,

Kuhlmann³

et al. 2008

Journal of Neuroscience

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The gene encoding DM20 emerged in cartilaginous fish, descending from a bilaterian ancestor of the M6 proteolipid gene family. Its proteolipid protein (PLP) isoform appeared in amphibians, contains an additional 35 amino acids, and, in the mammalian CNS, is the dominant myelin protein in which it confers an essential neuroprotective function. During development, the DM20 isoform is prominent in a number of tissues, and plp/DM20 transcripts are detected in multiple progenitor populations, including those that continue to express plp/DM20 as they differentiate into myelinating oligodendrocytes. The locus also encodes isoforms with extended leader sequences that accumulate in the cell bodies of several types of neurons. Here, to locate and characterize regulatory sequences controlling the complex plp/DM20 transcription program, putative regulatory sequences, suggested by interspecies conservation, were ligated individually to a minimally promoted eGFPlacZ reporter gene. These constructs were inserted in single copy at a common site adjacent to the hypoxanthine-guanine phosphoribosyltransferase locus in embryonic stem cells and their in vivo expression programs were compared in transgenic mice. Most expressed developmental and cell-specific subprograms accommodated within the known expression phenotype of the endogenous plp/DM20 locus, thus defining multiple components of the combinatorial mechanism controlling its normal temporal and cell-specific program. Along with previously characterized nervous system enhancers, those described here should help expose the content and configuration of elements that are operational in multiple glial and neuronal lineages. The transgenic lines derived here also provide effective markers for multiple stages of glial and neuronal lineage progression.

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Embryonic expression of myelin genes: Evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube

Cited by 231 publications

References 44 publications

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

Evidence That the Homeodomain Protein Gtx Is Involved in the Regulation of Oligodendrocyte Myelination

Trans-regulation of oligodendrocyte myelination by neurons through small GTPase Arf6-regulated secretion of fibroblast growth factor-2

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

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