Nuclear phosphatase PPM1G in cellular survival and neural development.

BACKGROUND:PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing, and DNA damage. However, its in vivo function is unknown. RESULTS:Here we show that ppm1g expression is highly enriched in the central nervous system during mouse and zebrafish development. ppm1g(-/-) mice were embryonic lethal with incomplete penetrance after E12.5. Rostral defects, including neural tube and craniofacial defects were observed in ppm1g(-/-) embryos associated with increased cell death in the neural epithelium. In zebrafish, loss of ppm1g also led to neural defects with aberrant neural marker gene expression. Primary fibroblasts from ppm1g(-/-) embryos failed to grow without immortalization while immortalized ppm1g(-/-) fibroblasts had increased cell death upon oxidative and genotoxic stress when compared to wild type fibroblasts. CONCLUSIONS:Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival.

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