Nuclear phosphatase PPM1G in cellular survival and neural development
- Authors
- Foster, W.H., Langenbacher, A., Gao, C., Chen, J., and Wang, Y.
- ID
- ZDB-PUB-130708-39
- Date
- 2013
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 242(9): 1101-9 (Journal)
- Registered Authors
- Langenbacher, Adam
- Keywords
- PPM1G, neural tube, serine threonine phosphatase, PP2Cγ
- 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
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/biosynthesis*
- Zebrafish Proteins/genetics
- PubMed
- 23723158 Full text @ Dev. Dyn.
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.
Conclusion
Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival.