Cargando…

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

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) o...

Descripción completa

Detalles Bibliográficos
Autores principales: Kaiser, Karol, Gyllborg, Daniel, Procházka, Jan, Salašová, Alena, Kompaníková, Petra, Molina, Francisco Lamus, Laguna-Goya, Rocio, Radaszkiewicz, Tomasz, Harnoš, Jakub, Procházková, Michaela, Potěšil, David, Barker, Roger A., Casado, Ángel Gato, Zdráhal, Zbyněk, Sedláček, Radislav, Arenas, Ernest, Villaescusa, J. Carlos, Bryja, Vítězslav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445127/
https://www.ncbi.nlm.nih.gov/pubmed/30940800
http://dx.doi.org/10.1038/s41467-019-09298-4
_version_ 1783408145243045888
author Kaiser, Karol
Gyllborg, Daniel
Procházka, Jan
Salašová, Alena
Kompaníková, Petra
Molina, Francisco Lamus
Laguna-Goya, Rocio
Radaszkiewicz, Tomasz
Harnoš, Jakub
Procházková, Michaela
Potěšil, David
Barker, Roger A.
Casado, Ángel Gato
Zdráhal, Zbyněk
Sedláček, Radislav
Arenas, Ernest
Villaescusa, J. Carlos
Bryja, Vítězslav
author_facet Kaiser, Karol
Gyllborg, Daniel
Procházka, Jan
Salašová, Alena
Kompaníková, Petra
Molina, Francisco Lamus
Laguna-Goya, Rocio
Radaszkiewicz, Tomasz
Harnoš, Jakub
Procházková, Michaela
Potěšil, David
Barker, Roger A.
Casado, Ángel Gato
Zdráhal, Zbyněk
Sedláček, Radislav
Arenas, Ernest
Villaescusa, J. Carlos
Bryja, Vítězslav
author_sort Kaiser, Karol
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6445127
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64451272019-04-03 WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis Kaiser, Karol Gyllborg, Daniel Procházka, Jan Salašová, Alena Kompaníková, Petra Molina, Francisco Lamus Laguna-Goya, Rocio Radaszkiewicz, Tomasz Harnoš, Jakub Procházková, Michaela Potěšil, David Barker, Roger A. Casado, Ángel Gato Zdráhal, Zbyněk Sedláček, Radislav Arenas, Ernest Villaescusa, J. Carlos Bryja, Vítězslav Nat Commun Article 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. Nature Publishing Group UK 2019-04-02 /pmc/articles/PMC6445127/ /pubmed/30940800 http://dx.doi.org/10.1038/s41467-019-09298-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kaiser, Karol
Gyllborg, Daniel
Procházka, Jan
Salašová, Alena
Kompaníková, Petra
Molina, Francisco Lamus
Laguna-Goya, Rocio
Radaszkiewicz, Tomasz
Harnoš, Jakub
Procházková, Michaela
Potěšil, David
Barker, Roger A.
Casado, Ángel Gato
Zdráhal, Zbyněk
Sedláček, Radislav
Arenas, Ernest
Villaescusa, J. Carlos
Bryja, Vítězslav
WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
title WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
title_full WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
title_fullStr WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
title_full_unstemmed WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
title_short WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
title_sort wnt5a is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445127/
https://www.ncbi.nlm.nih.gov/pubmed/30940800
http://dx.doi.org/10.1038/s41467-019-09298-4
work_keys_str_mv AT kaiserkarol wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT gyllborgdaniel wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT prochazkajan wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT salasovaalena wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT kompanikovapetra wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT molinafranciscolamus wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT lagunagoyarocio wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT radaszkiewicztomasz wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT harnosjakub wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT prochazkovamichaela wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT potesildavid wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT barkerrogera wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT casadoangelgato wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT zdrahalzbynek wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT sedlacekradislav wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT arenasernest wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT villaescusajcarlos wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis
AT bryjavitezslav wnt5aistransportedvialipoproteinparticlesinthecerebrospinalfluidtoregulatehindbrainmorphogenesis