RT Journal Article
SR Electronic
T1 ZFP423 regulates early patterning and multiciliogenesis in the hindbrain choroid plexus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.04.975573
DO 10.1101/2020.03.04.975573
A1 Filippo Casoni
A1 Laura Croci
A1 Francesca Vincenti
A1 Paola Podini
A1 Luca Massimino
A1 Ottavio Cremona
A1 G. Giacomo Consalez
YR 2020
UL http://biorxiv.org/content/early/2020/03/05/2020.03.04.975573.abstract
AB The choroid plexus (ChP) is a secretory tissue that produces cerebrospinal fluid (CSF) and secretes it into the ventricular system. CSF flows from the lateral to the third ventricle, and then to the fourth ventricle through the cerebral aqueduct. Recent studies have uncovered new, active roles for this structure in the regulation of neural stem cell maintenance and differentiation into neurons. Zfp423, encoding a Kruppel-type zinc finger transcription factor essential for cerebellar development and mutated in rare cases of cerebellar vermis hypoplasia / Joubert syndrome and other ciliopathies, is expressed in the hindbrain roof plate (RP), from which the IV ventricle ChP arises, and in mesenchymal cells giving rise to the stroma and leptomeninges. Zfp423 mutants display a marked reduction of the hindbrain ChP (hChP), which fails to express key markers of its secretory function and genes implicated in its development and maintenance (Lmx1a, Otx2). The mutant hChP displays a complete lack of multiciliated ependymal cells. A transcriptome analysis conducted at the earliest stages of hChP development and subsequent validations demonstrate that the mutant hChp displays a strong deregulation of pathways involved in early hindbrain patterning and multiciliated cell fate specification. Our results propose Zfp423 as a master gene and one of the earliest known determinants of hChP development.