WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 04 2019
02 04 2019
Historique:
received:
11
09
2017
accepted:
21
02
2019
entrez:
4
4
2019
pubmed:
4
4
2019
medline:
25
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30940800
doi: 10.1038/s41467-019-09298-4
pii: 10.1038/s41467-019-09298-4
pmc: PMC6445127
doi:
Substances chimiques
Lipoproteins
0
WNT5A protein, human
0
Wnt-5a Protein
0
Wnt5a protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1498Subventions
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
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