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

Karol Kaiser, Daniel Gyllborg, Jan Procházka, Alena Salašová, Petra Kompaníková, Francisco Lamus Molina, Rocio Laguna-Goya, Tomasz Radaszkiewicz, Jakub Harnoš, Michaela Procházková, David Potěšil, Roger A. Barker, Ángel Gato Casado, Zbyněk Zdráhal, Radislav Sedláček, Ernest Arenas (), J. Carlos Villaescusa () and Vítězslav Bryja ()
Additional contact information
Karol Kaiser: Faculty of Science, Masaryk University
Daniel Gyllborg: Karolinska Institutet
Jan Procházka: Institute of Molecular Genetics of the CAS, v. v. i., Prumyslova 595
Alena Salašová: Karolinska Institutet
Petra Kompaníková: Faculty of Science, Masaryk University
Francisco Lamus Molina: Universidad de Valladolid, Ramón y Cajal 5
Rocio Laguna-Goya: University of Cambridge
Tomasz Radaszkiewicz: Faculty of Science, Masaryk University
Jakub Harnoš: Faculty of Science, Masaryk University
Michaela Procházková: Institute of Molecular Genetics of the CAS, v. v. i., Prumyslova 595
David Potěšil: Central European Institute of Technology
Roger A. Barker: University of Cambridge
Ángel Gato Casado: Universidad de Valladolid, Ramón y Cajal 5
Zbyněk Zdráhal: Central European Institute of Technology
Radislav Sedláček: Institute of Molecular Genetics of the CAS, v. v. i., Prumyslova 595
Ernest Arenas: Karolinska Institutet
J. Carlos Villaescusa: Faculty of Science, Masaryk University
Vítězslav Bryja: Faculty of Science, Masaryk University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-09298-4

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