The transcription factor Otx2 regulates choroid plexus development and function.
Development 140, 1055-1066 (2013)
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
Typ der Hochschulschrift
Herausgeber
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2013
Prepublished im Jahr
HGF-Berichtsjahr
2013
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 140,
Heft: 5,
Seiten: 1055-1066
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Company of Biologists
Verlagsort
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
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Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30204 - Cell Programming and Repair
30201 - Metabolic Health
Forschungsfeld(er)
Stem Cell and Neuroscience
Genetics and Epidemiology
PSP-Element(e)
G-500800-001
G-500600-004
Förderungen
Copyright
Erfassungsdatum
2013-02-07