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Nat Commun. 2019 Apr 2;10(1):1498. doi: 10.1038/s41467-019-09298-4.

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

Author information

1
Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic.
2
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden.
3
Czech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CAS, v. v. i., Prumyslova 595, Vestec, 252 42, Czech Republic.
4
Danish Research Institute of Translational Neuroscience, Department of Biomedicine, Aarhus University, Aarhus, C 8000, Denmark.
5
Departamento de Anatomía y Radiología, Facultad de medicina, Universidad de Valladolid, Ramón y Cajal 5, 47005, Valladolid, Spain.
6
John van Geest Centre for Brain Repair and Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0PY, UK.
7
Central European Institute of Technology, 625 00, Brno, Czech Republic.
8
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden. ernest.arenas@ki.se.
9
Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic. carlos.villaescusa@gmail.com.
10
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden. carlos.villaescusa@gmail.com.
11
Psychiatric Stem Cell Group, Neurogenetics Unit, Center for Molecular Medicine, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm, 171 76, Sweden. carlos.villaescusa@gmail.com.
12
Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, 62500, Czech Republic. bryja@sci.muni.cz.

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.

PMID:
30940800
PMCID:
PMC6445127
DOI:
10.1038/s41467-019-09298-4
[Indexed for MEDLINE]
Free PMC Article

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