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Gajera, C.R.* ; Emich, H.* ; Lioubinski, O.* ; Christ, A.* ; Beckervordersandforth-Bonk, R. ; Yoshikawa, K.* ; Bachmann, S.* ; Christensen, E.I.* ; Götz, M. ; Kempermann, G.* ; Peterson, A.S.* ; Willnow, T.E.* ; Hammes, A.*

LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic niche.

J. Cell Sci. 123, 1922-1930 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The microenvironment of growth factors in the subependymal zone (SEZ) of the adult brain provides the instructive milieu for neurogenesis to proceed in this germinal niche. In particular, tight regulation of bone morphogenetic protein (BMP) signaling is essential to balance proliferative and non-proliferative cell fate specification. However, the regulatory pathways that control BMP signaling in the SEZ are still poorly defined. We demonstrate that LRP2, a clearance receptor for BMP4 is specifically expressed in ependymal cells of the lateral ventricles in the adult brain. Intriguingly, expression is restricted to the ependyma that faces the stem cell niche. Expression is not seen in ependyma elsewhere in the lateral ventricles or in the dentate gyrus, the second major neurogenic zone of the adult brain. We further show that lack of LRP2 expression in adult mice results in impaired proliferation of neural precursor cells in the SEZ resulting in decreased numbers of neuroblasts reaching the olfactory bulb. Reduced neurogenesis coincides with increased BMP4 expression and enhanced activation of downstream mediators phospho-SMAD1/5/8 and ID3 in the stem cell niche. Our findings suggest a novel mechanism whereby LRP2-mediated catabolism of BMP4 in the ependyma modulates the microenvironment of the SEZ and enables adult neurogenesis to proceed.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adult neurogenesis; LDL-receptor related receptors; Endocytosis; BMP4
ISSN (print) / ISBN 0021-9533
e-ISSN 1477-9137
Journal Journal of Cell Science
Quellenangaben Volume: 123, Issue: 11, Pages: 1922-1930 Article Number: , Supplement: ,
Publisher Company of Biologists
Publishing Place Cambridge
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)