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

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 co...

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Bibliographic Details
Published in:The Journal of neuroscience 2008-07, Vol.28 (27), p.6895-6903
Main Authors: Tuason, Maria Clarita, Rastikerdar, Ali, Kuhlmann, Tanja, Goujet-Zalc, Cecile, Zalc, Bernard, Dib, Samar, Friedman, Hana, Peterson, Alan
Format: Article
Language:English
Subjects:
Animals
Bilateria
Cell Differentiation - genetics
Cell Lineage - genetics
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Enhancer Elements, Genetic - genetics
Evolution, Molecular
Female
Gene Expression Regulation, Developmental - genetics
Genes, Reporter - genetics
Hypoxanthine Phosphoribosyltransferase - genetics
Life Sciences
Male
Mice
Mice, Transgenic
Myelin Proteolipid Protein - genetics
Nervous System - cytology
Nervous System - embryology
Nervous System - metabolism
Neuroglia - cytology
Neuroglia - metabolism
Neurons - cytology
Neurons - metabolism
Neurons and Cognition
Phenotype
Phylogeny
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4579-07.2008