Promoting Epiboly

Science's STKE  31 Jan 2006:
Vol. 2006, Issue 320, pp. tw46
DOI: 10.1126/stke.3202006tw46

Although steroids have numerous functions--regulating electrolyte balance; carbohydrate, protein, and fat metabolism; the inflammatory response; and the development and maintenance of secondary sex characteristics--their role during early embryogenesis has been unclear. Hsu et al. used in situ hybridization to investigate the expression of the genes encoding Cyp11a1 (which converts cholesterol to pregnenolone, thereby initiating steroid biosynthesis) and Hsd3b (which converts pregnenolone into progesterone) during zebrafish embryogenesis. Shortly after fertilization, mRNA for both enzymes was present in the cytoplasm of blastomeres located above the yolk. However, during epiboly (a process during which the blastoderm envelops the yolk), cyp11a1 and hsd3b disappeared from the blastomeres and appeared in the yolk syncytial layer, which is composed of yolk syncytial nuclei and located at the junction between the blastomeres and the yolk. Injection of antisense morpholino oligonucleotides to cyp11a1 delayed epiboly without affecting cell fate. Whereas coinjection of cyp11a1 mRNA or incubation with pregnenolone partially rescued the delay in epiboly, progesterone worsened it. Yolk microtubules extend from yolk syncytial nuclei to drive epiboly, and yolk microtubules from embryos treated with morpholinos were more sensitive to disruption by nocodazole than those from wild-type embryos, an effect that was reversed by pregnenolone. Pregnenolone also increased the abundance of polymerized tubulin in taxol-treated extracts from morpholino-treated embryos. Moreover, fluorescently labeled pregnenolone colocalized with polymerized tubulin from morpholino-treated embryo extracts. Thus, pregnenolone appears to stabilize microtubules and thereby promote cell migration during epiboly, a role that likely involves binding to microtubules rather than association with nuclear receptors.

H.-J. Hsu, M.-R. Liang, C.-T. Chen, B.-c. Chung, Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement. Nature 439, 480-483 (2006). [PubMed]