Wnt-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitosis in zebrafish

I. Castanon (), J. T. Hannich, L. Abrami, F. Huber, M. Dubois, M. Müller, F. G. van der Goot and M. Gonzalez-Gaitan ()
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I. Castanon: Department of Biochemistry and NCCR Chemical Biology, 30 Quai Ernest-Ansermet
J. T. Hannich: Department of Biochemistry and NCCR Chemical Biology, 30 Quai Ernest-Ansermet
L. Abrami: EPFL, Station 15
F. Huber: Vital-IT, SIB Swiss Institute of Bioinformatics
M. Dubois: Department of Biochemistry and NCCR Chemical Biology, 30 Quai Ernest-Ansermet
M. Müller: Vital-IT, SIB Swiss Institute of Bioinformatics
F. G. van der Goot: EPFL, Station 15
M. Gonzalez-Gaitan: Department of Biochemistry and NCCR Chemical Biology, 30 Quai Ernest-Ansermet

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Oriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divisions that are robustly oriented along the animal-vegetal embryonic axis. Here, we use a combination of lipidomics, metabolic tracer analysis and quantitative image analysis to show that sphingolipids mediate spindle positioning during oriented division of epiblast cells. We identify the Wnt signaling as a regulator of sphingolipid synthesis that mediates the activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid production. Sphingolipids determine the palmitoylation state of the Anthrax receptor, which then positions the mitotic spindle of dividing epiblast cells. Our data show how Wnt signaling mediates sphingolipid-dependent oriented division and how sphingolipids determine Anthrax receptor palmitoylation, which ultimately controls the activation of Diaphanous to mediate spindle rotation and oriented mitosis.

Date: 2020
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DOI: 10.1038/s41467-020-17196-3

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