The gene profile of zebrafish guanine binding protein-like 2 (Gnl2) mutant embryos versus wild-type embryos at 22 hours post-fertilization

ABSTRACT: Nucleostemin (NS), a member of a family of nucleolar GTP-binding proteins, is highly expressed in proliferating cells and implicated in the control of cell cycle progression, the maintenance of stem cells, and the regulation of cancer cells. The depletion of NS in cell lines and invertebrate animals has been demonstrated to result in defective ribosome biogenesis, while both depletion and overexpression of NS are able to stabilize the tumor suppressor p53 protein. While the existence of p53-independent functions of NS has been previously suggested, these roles to date remain unclear. Here, we report two zebrafish mutants recovered from forward and reverse genetic screens that encode two members of this nucleolar protein family, Guanine nucleotide binding-protein-like 2 (Gnl2) and Gnl3/Nucleostemin (Ns). We show that Gnl2 and Ns are required for pre-rRNA processing and the production of the 60S ribosomal subunit in the developing zebrafish embryo. In addition, we demonstrate that these proteins are required for correct timing of neural differentiation in the brain and retina. In both mutants, cell cycle regulators such as cyclinD1 and the cell cycle inhibitor cdkn1c/p57kip2 are aberrantly expressed. Concomitantly, retinal progenitors fail to exit the cell cycle in a timely fashion and differentiation of retinal cell types is delayed. We show that loss of either Gnl2 or Ns induces the stabilization of p53 and apoptosis in the brain, however the retinal cell differentiation defect in gnl2 mutants is independent of p53 status. This work demonstrates that the loss of either Gnl2 or Ns results in ribosome biogenesis and neural differentiation defects in vertebrates. In addition, the data suggests that the latter phenotype of gnl2 mutants is due to an increase in expression of cell cycle markers cyclinD1 and p57/kip2 and not to the stabilization of p53.

ORGANISM(S): Danio rerio

PROVIDER: GSE21134 | GEO | 2010/03/31

SECONDARY ACCESSION(S): PRJNA126649

REPOSITORIES: GEO