Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Biol Cell. 2011 Oct 1;103(10):483-98. doi: 10.1042/BC20110032.
pes1 (pescadillo homologue 1) and ppan (Peter Pan) are multifunctional proteins involved in ribosome biogenesis, cell proliferation, apoptosis, cell migration and regulation of gene expression. Both proteins are required for early neural development in Xenopus laevis, as previously demonstrated.
We show that the expression of both genes in the developing pronephros depends on wnt4 and fzd3 (frizzled homologue 3) function. Loss of pes1 or ppan by MO (morpholino oligonucleotide)-based knockdown approaches resulted in strong malformations during pronephric tubule formation. Defects were already notable during specification of pronephric progenitor cells, as shown by lhx1 expression. Moreover, we demonstrated that Xenopus pes1 and ppan interact physically and functionally and that pes1 and ppan can cross-rescue the loss of function phenotype of one another. Interference with rRNA synthesis, however, did not result in a similar early pronephros phenotype.
These results demonstrate that pes1 and ppan are required for Xenopus pronephros development and indicate that their function in the pronephros is independent of their role in ribosome biosynthesis.
pes1（pescadillo 同源物 1）和 ppan（Peter Pan）是多功能蛋白，参与核糖体生物发生、细胞增殖、细胞凋亡、细胞迁移和基因表达调控。如前所述，这两种蛋白质都对非洲爪蟾的早期神经发育至关重要。
我们表明，在发育中的前肾中，这两个基因的表达都依赖于 wnt4 和 fzd3（frizzled 同源物 3）的功能。通过基于 MO（morpholino oligonucleotide）的敲低方法敲低 pes1 或 ppan 的表达，在前肾小管形成过程中导致强烈的畸形。正如 lhx1 表达所示，在前肾祖细胞的特化过程中就已经出现了明显的缺陷。此外，我们证明了 Xenopus pes1 和 ppan 具有物理和功能相互作用，并且 pes1 和 ppan 可以相互交叉挽救彼此功能丧失的表型。然而，干扰 rRNA 合成并没有导致类似的早期前肾表型。
这些结果表明 pes1 和 ppan 是 Xenopus 前肾发育所必需的，并表明它们在前肾中的功能与其在核糖体生物合成中的作用是独立的。
