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Johansson, P.A. ; Irmler, I. ; Acampora, D.* ; Beckers, J. ; Simeone, A.* ; Götz, M.

The transcription factor Otx2 regulates choroid plexus development and function.

Development 140, 1055-1066 (2013)
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The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cerebral Cortex Development ; Cerebrospinal Fluid ; Wnt ; Mouse; Dorsal Telencephalic Midline ; Dopaminergic Progenitors ; Monodelphis-domestica ; Cerebrospinal-fluid ; Developing Brain ; Cerebral-cortex ; Sonic Hedgehog ; Roof Plate ; Fate ; Midbrain
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Band: 140, Heft: 5, Seiten: 1055-1066 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Begutachtungsstatus Peer reviewed