title: Evidence for NG2-glia derived, adult-born functional neurons in the hypothalamus.
abstract: Accumulating evidence suggests that the adult murine hypothalamus, a control site of several fundamental homeostatic processes, has neurogenic capacity. Correspondingly, the adult hypothalamus exhibits considerable cell proliferation that is ongoing even in the absence of external stimuli, and some of the newborn cells have been shown to mature into cells that express neuronal fate markers. However, the identity and characteristics of proliferating cells within the hypothalamic parenchyma have yet to be thoroughly investigated. Here we show that a subset of NG2-glia distributed throughout the mediobasal hypothalamus are proliferative and express the stem cell marker Sox2. We tracked the constitutive differentiation of hypothalamic NG2-glia by employing genetic fate mapping based on inducible Cre recombinase expression under the control of the NG2 promoter, demonstrating that adult hypothalamic NG2-glia give rise to substantial numbers of APC+ oligodendrocytes and a smaller population of HuC/D+ or NeuN+ neurons. Labelling with the cell proliferation marker BrdU confirmed that some NG2-derived neurons have proliferated shortly before differentiation. Furthermore, patch-clamp electrophysiology revealed that some NG2-derived cells display an immature neuronal phenotype and appear to receive synaptic input indicative of their electrical integration in local hypothalamic circuits. Together, our studies show that hypothalamic NG2-glia are able to take on neuronal fates and mature into functional neurons, indicating that NG2-glia contribute to the neurogenic capacity of the adult hypothalamus.
authors.affiliation: Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Robins
authors.forename: Eric
authors.initials: E
authors.lastname: Trudel
authors.forename: Olivia
authors.initials: O
authors.lastname: Rotondi
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.forename: Tina
authors.initials: T
authors.lastname: Djogo
authors.forename: Darya
authors.initials: D
authors.lastname: Kryzskaya
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
authors.forename: Maia V
authors.initials: MV
authors.lastname: Kokoeva
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D015415:Biomarkers; D001973:Bromodeoxyuridine; D019426:Integrases; D011509:Proteoglycans; D055748:SOXB1 Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C527783:Sox2 protein, mouse; C045073:Cre recombinase