C9C5 positive mature oligodendrocytes are a source of Sonic Hedgehog in the mouse brain

• Published in: PloS one Vol. 15; no. 2; p. e0229362
• Main Authors: Tirou, Linda, Russo, Mariagiovanna, Faure, Helene, Pellegrino, Giuliana, Sharif, Ariane, Ruat, Martial
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.02.2020; Public Library of Science (PLoS)
• Subjects: Aging; Animals; Antibodies; Antibodies, Monoclonal - immunology; Astrocytes; Biology and Life Sciences; Brain; Brain - immunology; Brain - metabolism; Carbonic anhydrase; Carbonic anhydrase II; Cell body; Cells (biology); Cells, Cultured; Cellular Biology; Circuits; Cytogenetics; Development Biology; Experiments; Fluorescence; Fluorescence in situ hybridization; Glial fibrillary acidic protein; Glial stem cells; Hedgehog protein; Hedgehog Proteins - immunology; Hedgehog Proteins - metabolism; HEK293 Cells; Humans; Immunoreactivity; Life Sciences; Male; Markers; Medicine and Health Sciences; Messenger RNA; Mice; Mice, Inbred C57BL; Myelination; Neural stem cells; Neuronal-glial interactions; Neurons; Neurons - immunology; Neurons - metabolism; Neurons and Cognition; Neurosciences; Olig2 protein; Oligodendrocytes; Oligodendroglia - immunology; Oligodendroglia - metabolism; Patched Receptors - immunology; Patched Receptors - metabolism; Pattern recognition; Progenitor cells; Proteins; Research and Analysis Methods; Rodents; Signal transduction; Sox10 protein; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229362

In the mature rodent brain, Sonic Hedgehog (Shh) signaling regulates stem and progenitor cell maintenance, neuronal and glial circuitry and brain repair. However, the sources and distribution of Shh mediating these effects are still poorly characterized. Here, we report in the adult mouse brain, a broad expression pattern of Shh recognized by the specific monoclonal C9C5 antibody in a subset (11-12%) of CC1+ mature oligodendrocytes that do not express carbonic anhydrase II. These cells express also Olig2 and Sox10, two oligodendrocyte lineage-specific markers, but not PDGFRα, a marker of oligodendrocyte progenitors. In agreement with oligodendroglial cells being a source of Shh in the adult mouse brain, we identify Shh transcripts by single molecule fluorescent in situ hybridization in a subset of cells expressing Olig2 and Sox10 mRNAs. These findings also reveal that Shh expression is more extensive than originally reported. The Shh-C9C5-associated signal labels the oligodendroglial cell body and decorates by intense puncta the processes. C9C5+ cells are distributed in a grid-like manner. They constitute small units that could deliver locally Shh to its receptor Patched expressed in GFAP+ and S100β+ astrocytes, and in HuC/D+ neurons as shown in PtcLacZ/+ reporter mice. Postnatally, C9C5 immunoreactivity overlaps the myelination peak that occurs between P10 and P20 and is down regulated during ageing. Thus, our data suggest that C9C5+CC1+ oligodendroglial cells are a source of Shh in the mouse postnatal brain.