Developmental Activation of the Proteolipid Protein Promoter Transgene in Neuronal and Oligodendroglial Cells of Neostriatum in Mice

• Published in: Developmental neuroscience Vol. 33; no. 2; pp. 170 - 184
• Main Authors: Fulton, Daniel, Paez, Pablo, Spreur, Vilma, Handley, Vance, Colwell, Christopher S., Campagnoni, Anthony, Fisher, Robin
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.09.2011
• Subjects: Animals; Animals, Newborn; Brain - growth & development; Brain - metabolism; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Humans; Mice; Mice, Transgenic; Myelin Proteolipid Protein - genetics; Myelin Proteolipid Protein - metabolism; Myelin Sheath - metabolism; Neostriatum - metabolism; Neurons - metabolism; Oligodendroglia - cytology; Oligodendroglia - metabolism; Original Paper; Protein Isoforms - genetics; Protein Isoforms - metabolism; Transgenes; Morphogenesis; Basal ganglia; Cell lineage markers in immature neostriatum; Soma-restricted and classic proteolipid protein isoforms; Myelin proteins; EGFP reporter; Electrophysiological development
• ISSN: 0378-5866; 1421-9859
• DOI: 10.1159/000330321

Prior studies suggest that non-canonical proteolipid protein (PLP) gene expression occurs during development in non-myelinating neurons as well as myelinating oligodendroglia in mammalian brain. To assess this possibility in neostriatum, a region of uncertain PLP gene expression in neurons, morphological and electrophysiological tools were used to determine phenotypes of cells with activation of a PLP promoter transgene during the early postnatal period in mice. PLP gene expression is evident in both neuronal and oligodendroglial phenotypes in developing neostriatum, a conclusion based on three novel observations: (1) An enhanced green fluorescent protein (EGFP) reporter of PLP promoter activation was localized in two distinct populations of cells, which exhibit collective, developmental differences of morphological and electrophysiological characteristics in accord with neuronal and oligodendroglial phenotypes of neostriatal cells found during the early postnatal period in both transgenic and wild-type mice. (2) The EGFP reporter of PLP promoter activation was appropriately positioned to serve as a regulator of PLP gene expression. It colocalized with native PLP proteins in both neuronal and oligodendroglial phenotypes; however, only soma-restricted PLP protein isoforms were found in the neuronal phenotype, while classic and soma-restricted PLP protein isoforms were found in the oligodendroglial phenotype. (3) As shown by EGFP reporter, PLP promoter activation was placed to regulate PLP gene expression in only one neuronal phenotype among the several that constitute neostriatum. It was localized in medium spiny neurons, but not large aspiny neurons. These outcomes have significant implications for the non-canonical functional roles of PLP gene expression in addition to myelinogenesis in mammalian brain, and are consistent with potentially independent pathologic loci in neurons during the course of human mutational disorders of PLP gene expression.