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

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

doi:10.1038/s41467-019-09298-4

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

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

^*Corresponding author for this work

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63 Citations (Scopus)

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.

Original language	English
Article number	1498
Journal	Nature Communications
Volume	10
Issue	1
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-09298-4
Publication status	Published - 2019

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Kaiser, K., Gyllborg, D., Procházka, J., Salašová, A., Kompaníková, P., Molina, F. L., Laguna-Goya, R., Radaszkiewicz, T., Harnoš, J., Procházková, M., Potěšil, D., Barker, R. A., Casado, Á. G., Zdráhal, Z., Sedláček, R., Arenas, E., Villaescusa, J. C., & Bryja, V. (2019). WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis. Nature Communications, 10(1), Article 1498. https://doi.org/10.1038/s41467-019-09298-4

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title = "WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis",

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.",

author = "Karol Kaiser and Daniel Gyllborg and Jan Proch{\'a}zka and Alena Sala{\v s}ov{\'a} and Petra Kompan{\'i}kov{\'a} and Molina, {Francisco Lamus} and Rocio Laguna-Goya and Tomasz Radaszkiewicz and Jakub Harno{\v s} and Michaela Proch{\'a}zkov{\'a} and David Pot{\v e}{\v s}il and Barker, {Roger A.} and Casado, {{\'A}ngel Gato} and Zbyn{\v e}k Zdr{\'a}hal and Radislav Sedl{\'a}{\v c}ek and Ernest Arenas and Villaescusa, {J. Carlos} and V{\'i}t{\v e}zslav Bryja",

year = "2019",

doi = "10.1038/s41467-019-09298-4",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Kaiser, K, Gyllborg, D, Procházka, J, Salašová, A, Kompaníková, P, Molina, FL, Laguna-Goya, R, Radaszkiewicz, T, Harnoš, J, Procházková, M, Potěšil, D, Barker, RA, Casado, ÁG, Zdráhal, Z, Sedláček, R, Arenas, E, Villaescusa, JC & Bryja, V 2019, 'WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis', Nature Communications, vol. 10, no. 1, 1498. https://doi.org/10.1038/s41467-019-09298-4

WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis. / Kaiser, Karol; Gyllborg, Daniel; Procházka, Jan et al.
In: Nature Communications, Vol. 10, No. 1, 1498, 2019.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis

AU - Kaiser, Karol

AU - Gyllborg, Daniel

AU - Procházka, Jan

AU - Salašová, Alena

AU - Kompaníková, Petra

AU - Molina, Francisco Lamus

AU - Laguna-Goya, Rocio

AU - Radaszkiewicz, Tomasz

AU - Harnoš, Jakub

AU - Procházková, Michaela

AU - Potěšil, David

AU - Barker, Roger A.

AU - Casado, Ángel Gato

AU - Zdráhal, Zbyněk

AU - Sedláček, Radislav

AU - Arenas, Ernest

AU - Villaescusa, J. Carlos

AU - Bryja, Vítězslav

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-019-09298-4

DO - 10.1038/s41467-019-09298-4

M3 - Journal article

C2 - 30940800

AN - SCOPUS:85063737300

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1498

ER -

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

Abstract

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