Publication details

WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis

Authors

KAISER Karol GYLLBORG D. PROCHAZKA J. SALAŠOVÁ Alena KOMPANÍKOVÁ Petra MOLINA F.L. LAGUNA-GOYA R. RADASZKIEWICZ Tomasz Witold HARNOŠ Jakub PROCHAZKOVA M. POTĚŠIL David BARKER R.A. CASADO A.G. ZDRÁHAL Zbyněk SEDLACEK R. ARENAS E. VILLAESCUSA Juan Carlos BRYJA Vítězslav

Year of publication 2019
Type Article in Periodical
Magazine / Source Nature Communications
MU Faculty or unit

Faculty of Science

Citation
Web https://www.nature.com/articles/s41467-019-09298-4
Doi http://dx.doi.org/10.1038/s41467-019-09298-4
Keywords LOW-DENSITY LIPOPROTEINS; CELLS; PROTEINS; RECEPTOR; EXPRESSION; MUTATIONS; SECRETION; PROTEOME; HEDGEHOG; SYSTEM
Description WNTs are lipid-modified proteins that control multiple functions in development and disease via short- and long-range signaling. However, it is unclear how these hydrophobic molecules spread over long distances in the mammalian brain. Here we show that WNT5A is produced by the choroid plexus (ChP) of the developing hindbrain, but not the telencephalon, in both mouse and human. Since the ChP produces and secretes the cerebrospinal fluid (CSF), we examine the presence of WNT5A in the CSF and find that it is associated with lipoprotein particles rather than exosomes. Moreover, since the CSF flows along the apical surface of hindbrain progenitors not expressing Wnt5a, we examined whether deletion of Wnt5a in the ChP controls their function and find that cerebellar morphogenesis is impaired. Our study thus identifies the CSF as a route and lipoprotein particles as a vehicle for long-range transport of biologically active WNT in the central nervous system.
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