Oligodendrocyte development in the embryonic tuberal hypothalamus and the influence of Ascl1. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Marsters, Candace; Rosin, Jessica; Thornton, Hayley; Aslanpour, Shaghayegh; Klenin, Natasha; Wilkinson, Grey; Schuurmans, Carol; Pittman, Quentin; Kurrasch, Deborah
• Is Part Of: Neural development. Volume 11:Issue 1(2016)
• Page Start: 1
• Page End: 15
• Publication Date: 2016-12
• Subjects: Gliogenesis -- Oligodendrogenesis -- Astrocyte -- Ascl1 -- Neurog2 -- Sox9 -- Olig2 -- PdgfRα; Neurology -- Periodicals; Nervous system -- Growth -- Periodicals; Developmental neurobiology -- Periodicals; 573.8
• DOI: 10.1186/s13064-016-0075-9
• Languages: English
• ISSNs: 1749-8104

Abstract

Abstract Background Although the vast majority of cells in our brains are glia, we are only beginning to understand programs governing their development, especially within the embryonic hypothalamus. In mice, gliogenesis is a protracted process that begins during embryonic stages and continues into the early postnatal period, with glial progenitors first producing oligodendrocyte precursor cells, which then differentiate into pro-oligodendrocytes, pro-myelinating oligodendrocytes, and finally, mature myelinating oligodendrocytes. The exact timing of the transition from neurogenesis to gliogenesis and the subsequent differentiation of glial lineages remains unknown for most of the Central Nervous System (CNS), and is especially true for the hypothalamus. Methods Here we used mouse embryonic brain samples to determine the onset of gliogenesis and expansion of glial populations in the tuberal hypothalamus using glial markers Sox9, Sox10, Olig2, PdgfRα, Aldh1L1, and MBP. We further employedAscl1 andNeurog2 mutant mice to probe the influence of these proneual genes on developing embryonic gliogenic populations. Results Using marker analyses for glial precursors, we found that gliogenesis commences just prior to E13.5 in the tuberal hypothalamus, beginning with the detection of glioblast and oligodendrocyte precursor cell markers in a restricted domain adjacent to the third ventricle. Sox9+ and Olig2+ glioblasts are also observed in the mantle region from E13.5 onwards, many of which are Ki67+ proliferating cells, and peaks at E17.5. UsingAscl1 andNeurog2 mutant mice to investigate the influence of these bHLH transcription factors on the progression of gliogenesis in the tuberal hypothalamus, we found that the elimination ofAscl1 resulted in an increase in oligodendrocyte cells throughout the expansive period of oligodendrogenesis. Conclusion Our results are the first to define the timing of gliogenesis in the tuberal hypothalamus and indicate that Ascl1 is required to repress oligodendrocyte differentiation within this brain region.