Our article has been chosen by the Development editor Paola Arlotta (Harvard Stem Cell Institute) and selected for the monthly webinar „Development presents ….“ !
The topic will be introduced by the first author Karol Kaiser, Ph.D.:
„MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus“
on Wednesday 12th of May, at 17.00.
If you are interested, register here: https://thenode.biologists.com/development-presents-may-webinar/development-presents/
Title of the paper: MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus
Karol Kaiser, Ahram Jang, Petra Kompaníková, Melody P. Lun, Jan Procházka, Ondrej Machon, Neil Dani, Michaela Procházková, Benoit Laurent, Daniel Gyllborg, Renée van Amerongen, , Ryann M. Fame, Suhasini Gupta, Feizhen Wu, Roger A. Barker, Ivana Buková, Radislav Sedláček, Zbyněk Kozmík, Ernest Arenas, Maria K. Lehtinen* and Vítězslav Bryja*
The choroid plexus (ChP) produces cerebrospinal fluid and forms a critical 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 critical for determining fourth ventricle (4V) ChP morphogenesis and size. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at E10.5, 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 noncanonical Wnt signaling via Ror1/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.
Link to the preprint of the paper: https://www.biorxiv.org/content/10.1101/2020.05.07.082370v1
Accepted in Development.