Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement.
Embryonic cell movement is essential for morphogenesis and the establishment of body shapes, but little is known about its mechanism. Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting cell migration during epiboly. Epiboly is a process in which embryonic cells spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1 is expressed in an extra-embryonic yolk syncytial layer. Reducing cyp11a1 expression in zebrafish using antisense morpholino oligonucleotides did not perturb cell fates, but caused epibolic delay. This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. We show that the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. Our results indicate that pregnenolone preserves microtubule abundance and promotes cell movement during epiboly.
Hsu
Hwei-Jan
HJ
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan.
Liang
Ming-Ren
MR
Chen
Chao-Tsen
CT
Chung
Bon-chu
BC
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001757:Blastomeres / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000187:drug effects* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D029961:Zebrafish Proteins; D011284:Pregnenolone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme