Genetic Evidence for the Gatekeeping Role of Ybx1 in Controlling Follicle Activation and Early Folliculogenesis by Regulation of Cdkn1a in the Zebrafish
Ontology highlight
ABSTRACT: Y box-binding protein 1 (YB-1; Ybx1/ybx1) regulates transcription and translation of targeted genes by DNA/RNA-binding. Our previous proteomic study demonstrated a dramatic drop in Ybx1 protein during follicle activation in zebrafish ovary. In this study, we created an ybx1 mutant with CRISPR/Cas9, and showed that the folliculogenesis in the mutant ovary (ybx1-/-) was blocked at pre-vitellogenic (PV)-to-early vitellogenic (EV) transition, leading to small ovaries. The mutant females were therefore sub-fertile with reduced fecundity. RNA-seq and Western blot analyses identified a variety of genes that showed differential expression between mutant ovary (ybx1-/-) and the control (ybx1+/-) including cdkn1a (p21). Disruption of cdkn1a resulted in embryonic lethality. In p21 heterozygotes (cdkn1a+/-), however, follicle activation and maturation in the ovary were both enhanced in contrast to ybx1 mutant (ybx1-/-). Interestingly, partial loss of p21 in heterozygotes (cdkn1a+/-) could rescue the phenotype of ybx1 mutant (ybx1-/-). Folliculogenesis resumed in ybx1-/-;p21+/- females with normal follicle activation, in contrast to the PV-EV blockade in ybx1-/- mutant. Interestingly, the follicle cells from the ybx1-/- mutant follicles displayed a poor proliferative activity in vitro; however, the cells from the ybx1-/-p21+/- follicles resumed normal proliferation compared to that from the wildtype fish. In summary, we demonstrated in this study that Ybx1 played a gatekeeping role in controlling PV-to-EV transition and it might act by suppressing the expression of cdkn1a, a cell cycle inhibitor.
ORGANISM(S): Danio rerio
PROVIDER: GSE239623 | GEO | 2024/10/27
REPOSITORIES: GEO
ACCESS DATA