Novel mode of long-range transport of Wnts published in Nature Communications!

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 & Vítězslav Bryja

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 expressingWnt5a, we examined whether deletion ofWnt5ain theChP 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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