PUBLICATION

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

Authors
Castanon, I., Hannich, J.T., Abrami, L., Huber, F., Dubois, M., Müller, M., van der Goot, F.G., Gonzalez-Gaitan, M.
ID
ZDB-PUB-200706-2
Date
2020
Source
Nature communications   11: 3317 (Journal)
Registered Authors
Castanon, Irinka
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Asymmetric Cell Division/genetics
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism*
  • Gastrulation
  • Gene Expression Regulation, Developmental
  • Germ Layers/cytology
  • Germ Layers/embryology
  • Germ Layers/metabolism
  • Lipoylation
  • Mitosis*
  • Neural Tube/cytology
  • Neural Tube/embryology
  • Neural Tube/metabolism
  • Receptors, Peptide/genetics
  • Receptors, Peptide/metabolism*
  • Sequence Homology, Amino Acid
  • Serine C-Palmitoyltransferase/genetics
  • Serine C-Palmitoyltransferase/metabolism
  • Sphingolipids/metabolism*
  • Spindle Apparatus/metabolism
  • Wnt Signaling Pathway*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
32620775 Full text @ Nat. Commun.
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.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping