The role of protein phosphatase 2A during mouse embryogenesis
Description
During development, growth factor mediated signaling controls processes that are required for the proper growth and patterning of organs, intracellular protein phosphorylation is a common mechanism used to regulate these growth factors signaling events during development. While the regulation of growth factor signaling by protein kinases is well-characterized, the role of protein phosphatases in regulating growth factor signaling events has only recently begun to be investigated. The data presented demonstrate the importance of the Ser/The phosphatase, PP2A in regulating embryonic mouse development. The murine homologue of the PP2A catalytic subunit alpha (pp2Acalpha ) was cloned and its expression during postimplantation mouse embryogenesis was characterized. Northern blot analyses demonstrated that pp2Acalpha was expressed as a 2kb transcript throughout embryonic development, and the level of pp2Acalpha expression was relatively uniform from E7.5--16.5 and then dramatically decreased at E17.5--18.5. In situ hybridization revealed that, while pp2Acalpha was initially expressed in a diffuse pattern, its expression became progressively concentrated in mesodermal tissues, including the tooth germ and limb, and in endodermal tissues, including the epithelial linings of the ethmoid sinus and the gut. By pharmacologically blocking the PP2A enzymatic activity in mandibular explant cultures, tooth development was arrested at the initiation stage, and the induction of the SHH target gene, ptc1, was blocked. Pharmacologically inhibition of PP2A activity in the mouse posterior limb bud 2.1 cells conferred polarizing activity to these cells, and transplantation of these cells into the anterior chick limb bud resulted in the production of an ectopic digit 2. These results indicate that PP2A may play an important regulatory role during the development of both the tooth and the limb