PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice

• Published in: Nature neuroscience Vol. 11; no. 12; pp. 1392 - 1401
• Main Authors: Rivers, Leanne E, Rizzi, Matteo, Psachoulia, Konstantina, Kessaris, Nicoletta, Wade, Anna, Richardson, William D, Young, Kaylene M, Jamen, Françoise
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2008; Nature Publishing Group
• Subjects: 2',3'-Cyclic-Nucleotide Phosphodiesterases - metabolism; Adult Stem Cells - drug effects; Adult Stem Cells - physiology; Animal Genetics and Genomics; Animals; Antibodies; Antigens - metabolism; Artificial chromosomes; Basic Helix-Loop-Helix Transcription Factors - metabolism; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Blood platelets; Bromodeoxyuridine - metabolism; Cell cycle; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell division; Cerebral Cortex - cytology; Cerebral Cortex - physiology; Estrogen Antagonists - pharmacology; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Humans; Luminescent Proteins - biosynthesis; Luminescent Proteins - genetics; Mice; Mice, Transgenic; Myelin Basic Protein - metabolism; Myelination; Nerve Tissue Proteins - metabolism; Neural Pathways - physiology; Neurobiology; Neurons - physiology; Neurosciences; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Oligodendroglia - physiology; Phosphopyruvate Hydratase - metabolism; Physiological aspects; Proteins - genetics; Proteins - metabolism; Proteoglycans - metabolism; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - physiology; Receptors; RNA, Untranslated; SOXE Transcription Factors - metabolism; Tamoxifen - pharmacology; United Kingdom; United Kingdom > UK
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.2220

About 4% of the cells in the adult rodent brain are PDGFRA + NG2 + glia, derived from the oligodendrocyte lineage. Rivers and colleagues constructed a transgenic mouse to fate map the PDGFRA + glia. In the adult corpus callosum, these cells generated substantial numbers of late-myelinating oligodendrocytes. In the cortex, little late myelination was observed; instead, PDGFRA + precursors seemed to continuously generate small numbers of projection neurons mainly in piriform cortex. Platelet-derived growth factor α receptor (PDGFRA)/NG2–expressing glia are distributed throughout the adult CNS. They are descended from oligodendrocyte precursors (OLPs) in the perinatal CNS, but it is not clear whether they continue to generate myelinating oligodendrocytes or other differentiated cells during normal adult life. We followed the fates of adult OLPs in Pdgfra-creER T2 /Rosa26-YFP double-transgenic mice and found that they generated many myelinating oligodendrocytes during adulthood; >20% of all oligodendrocytes in the adult mouse corpus callosum were generated after 7 weeks of age, raising questions about the function of the late-myelinating axons. OLPs also produced some myelinating cells in the cortex, but the majority of adult-born cortical cells did not appear to myelinate. We found no evidence for astrocyte production in gray or white matter. However, small numbers of projection neurons were generated in the forebrain, especially in the piriform cortex, which is the main target of the olfactory bulb.