Wnt/β-catenin signaling regulates ependymal cell development and adult homeostasis.

TitleWnt/β-catenin signaling regulates ependymal cell development and adult homeostasis.
Publication TypeJournal Article
Year of Publication2018
AuthorsXing L, Anbarchian T, Tsai JM, Plant GW, Nusse R
JournalProceedings of the National Academy of Sciences of the United States of America
Date Published2018 Jun 11
ISSN0027-8424
AbstractIn the adult mouse spinal cord, the ependymal cell population that surrounds the central canal is thought to be a promising source of quiescent stem cells to treat spinal cord injury. Relatively little is known about the cellular origin of ependymal cells during spinal cord development, or the molecular mechanisms that regulate ependymal cells during adult homeostasis. Using genetic lineage tracing based on the Wnt target gene , we have characterized Wnt-responsive cells during spinal cord development. Our results revealed that Wnt-responsive progenitor cells are restricted to the dorsal midline throughout spinal cord development, which gives rise to dorsal ependymal cells in a spatially restricted pattern. This is contrary to previous reports that suggested an exclusively ventral origin of ependymal cells, suggesting that ependymal cells may retain positional identities in relation to their neural progenitors. Our results further demonstrated that in the postnatal and adult spinal cord, all ependymal cells express the Wnt/β-catenin signaling target gene , as well as Wnt ligands. Genetic elimination of β-catenin or inhibition of Wnt secretion in Axin2-expressing ependymal cells in vivo both resulted in impaired proliferation, indicating that Wnt/β-catenin signaling promotes ependymal cell proliferation. These results demonstrate the continued importance of Wnt/β-catenin signaling for both ependymal cell formation and regulation. By uncovering the molecular signals underlying the formation and regulation of spinal cord ependymal cells, our findings thus enable further targeting and manipulation of this promising source of quiescent stem cells for therapeutic interventions.
URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=29891676
DOI10.1073/pnas.1803297115
Short TitleProc Natl Acad Sci U S A