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

0522728 - ÚMG 2020 RIV GB eng J - Článek v odborném periodiku
Kaiser, K. - Gyllborg, D. - Procházka, Jan - Salasova, A. - Kompanikova, P. - Molina, F. L. - Laguna-Goya, R. - Radaszkiewicz, T. - Harnoš, J. - Procházková, Michaela - Potěšil, D. - Barker, R. A. - Casado, A. G. - Zdráhal, Z. - Sedláček, Radislav - Arenas, E. - Villaescusa, J.C. - Bryja, V.
WNT5A is transported via lipoprotein particles in the cerebrospinal fluid to regulate hindbrain morphogenesis.
Nature Communications. Roč. 10, č. 1 (2019), č. článku 1498. E-ISSN 2041-1723
Grant CEP: GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395
Institucionální podpora: RVO:68378050
Klíčová slova: low-density lipoproteins * cells * proteins * receptor * expression * mutations * secretion * proteome * hedgehog * system
Obor OECD: Developmental biology
Impakt faktor: 12.121, rok: 2019
Způsob publikování: Open access
https://www.nature.com/articles/s41467-019-09298-4

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.
Trvalý link: http://hdl.handle.net/11104/0307175