Protein Serine/Threonine Phosphotase-1 is Essential in Governing Normal Development of Vertebrate Eye

Protein serine/threonine phosphatase-1 (PP1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP1 with morpholino oligomers leads to partial (PPl knockdown) or complete (PPl or PPl knockdown) death of the injected embryos. The survived embryos from PP1 knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream target mediating the effects of PP1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.