PUBLICATION

Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement

Authors
Hsu, H.J., Liang, M.R., Chen, C.T., and Chung, B.C.
ID
ZDB-PUB-060130-8
Date
2006
Source
Nature   439(7075): 480-483 (Journal)
Registered Authors
Chung, Bon-chu, Liang, Mei-Rong
Keywords
none
MeSH Terms
  • 3-Hydroxysteroid Dehydrogenases/genetics
  • 3-Hydroxysteroid Dehydrogenases/metabolism
  • Animals
  • Blastomeres/metabolism
  • Cell Movement/drug effects*
  • Cholesterol Side-Chain Cleavage Enzyme/genetics
  • Cholesterol Side-Chain Cleavage Enzyme/metabolism
  • Embryo, Nonmammalian/cytology*
  • Embryo, Nonmammalian/drug effects*
  • Embryo, Nonmammalian/embryology
  • Gene Expression Regulation, Developmental
  • Microtubules/drug effects*
  • Microtubules/metabolism
  • Pregnenolone/metabolism
  • Pregnenolone/pharmacology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
16437115 Full text @ Nature
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes