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

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  • Karol Kaiser, Karolinska Institutet
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  • Daniel Gyllborg, Karolinska Institutet
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  • Jan Procházka, Institute of Molecular Genetics of the CAS
  • ,
  • Alena Salašová
  • Petra Kompaníková, Masaryk University
  • ,
  • Francisco Lamus Molina, Universidad de Valladolid, Facultad de Medicina
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  • Rocio Laguna-Goya, Wellcome Trust-MRC Stem Cell Institute
  • ,
  • Tomasz Radaszkiewicz, Masaryk University
  • ,
  • Jakub Harnoš, Masaryk University
  • ,
  • Michaela Procházková, Institute of Molecular Genetics of the CAS
  • ,
  • David Potěšil, Central European Institute of Technology
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  • Roger A. Barker, Wellcome Trust-MRC Stem Cell Institute
  • ,
  • Ángel Gato Casado, Universidad de Valladolid, Facultad de Medicina
  • ,
  • Zbyněk Zdráhal, Central European Institute of Technology
  • ,
  • Radislav Sedláček, Institute of Molecular Genetics of the CAS
  • ,
  • Ernest Arenas, Karolinska Institutet
  • ,
  • J. Carlos Villaescusa, Karolinska Institutet
  • ,
  • Vítězslav Bryja, Masaryk University

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.

OriginalsprogEngelsk
Artikelnummer1498
TidsskriftNature Communications
Vol/bind10
Nummer1
ISSN2041-1723
DOI
StatusUdgivet - 2019

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