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

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• Oriented cell division is crucial for embryonic development, including neural tube formation and body axis extension.
• During zebrafish gastrulation, epiblast cells exhibit divisions oriented along the animal-vegetal axis.

Purpose of the Study:

• To investigate the role of sphingolipids in mediating spindle positioning during oriented cell division in zebrafish epiblast cells.
• To elucidate the regulatory pathway involving Wnt signaling, sphingolipid synthesis, and mitotic spindle orientation.

Main Methods:

• Lipidomics analysis
• Metabolic tracer analysis
• Quantitative image analysis

Main Results:

• Sphingolipids were identified as key mediators of spindle positioning in oriented epiblast cell division.
• Wnt signaling regulates sphingolipid synthesis by modulating serine palmitoyltransferase (SPT) activity.
• Sphingolipids control the palmitoylation of the Anthrax receptor, which is essential for mitotic spindle positioning and oriented division.

Conclusions:

• Wnt signaling promotes sphingolipid-dependent oriented cell division through regulation of Anthrax receptor palmitoylation.
• This pathway ultimately controls Diaphanous activation, mediating spindle rotation and oriented mitosis in zebrafish embryos.