MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus

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Authors

KAISER Karol JANG Ahram KOMPANÍKOVÁ Petra LUN Melody P. PROCHAZKA Jan MACHON Ondrej DANI Neil PROCHAZKOVA Michaela LAURENT Benoit GYLLBORG Daniel VAN AMERONGEN Renee FAME Ryann M. GUPTA Suhasini WU Feizhen BARKER Roger A. BUKOVA Ivana SEDLACEK Radislav KOZMIK Zbynek ARENAS Ernest LEHTINEN Maria K. BRYJA Vítězslav

Year of publication 2021
Type Article in Periodical
Magazine / Source Development
MU Faculty or unit

Faculty of Science

Citation
Web https://journals.biologists.com/dev/article/148/10/dev192054/268365/MEIS-WNT5A-axis-regulates-development-of-fourth
Doi http://dx.doi.org/10.1242/dev.192054
Keywords Choroid plexus; Epithelium; Meis1; Meis2; Morphogenesis; WNT5a
Description The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at embryonic day 10.5, profoundly reduced ChP size and development. However, Wnt5a expression was enriched in Foxj1-positive epithelial cells of 4V ChP plexus, and its conditional deletion in these cells affected the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical WNT signaling via ROR1 and ROR2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS transcription factors as upstream regulators of Wnt5a in the 4V ChP epithelium.
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