Nuclear phosphatase PPM1G in cellular survival and neural development

Dev Dyn. 2013 Sep;242(9):1101-9. doi: 10.1002/dvdy.23990. Epub 2013 Jul 26.

Abstract

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.

Keywords: PPM1G; neural tube; serine threonine phosphatase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Cell Survival / physiology
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Neural Tube / cytology
  • Neural Tube / embryology*
  • Neural Tube / enzymology
  • Neurogenesis / physiology*
  • Phosphoprotein Phosphatases / biosynthesis*
  • Phosphoprotein Phosphatases / genetics
  • Protein Phosphatase 2C
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / biosynthesis*
  • Zebrafish Proteins / genetics

Substances

  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2C