A recent study published in the journal Cell Reports reveals that the famous tumor suppressor gene p53 and the development of neural tubes in female embryos are surprisingly critical. The study suggests that p53 is involved in a female-specific molecular process called “X chromosome inactivation”. The new findings help explain why women are more likely to be born with neural tube birth defects than men.
Neural tube defects (NTDs), such as extracerebral malformation and spina bifida, which are one of the most common developmental defects in human beings, and most of them are found in women. NTDs is the result of neural tube closure failure during embryogenesis. Successful neural tube closure requires the complex interaction of several cellular and morphological processes, which are still not completely clear.
A recent study published in the journal Cell Reports reveals that the famous tumor suppressor gene p53 and the development of neural tubes in female embryos are surprisingly critical. The study suggests that p53 is involved in a female-specific molecular process called “X chromosome inactivation”. The new findings help explain why women are more likely to be born with neural tube birth defects than men. The study was led by Associate Professor Anne Voss, Professor Andreas Strasser and Associate Professor Marnie Blewitt at the Walter and Eliza Hall Institute of Medicine, in collaboration with researchers at the Peter MacCallum Cancer Center.
Professor Strasser says studies have shown that p53 affects the function of genes needed to promote the production of healthy neural tube cells in female embryos. He added “Healthy neural tube development is a very precise and unstable balance process, P53 helps female embryos achieve this balance by producing normal levels of Xist RNA, which as part of a complex molecular process that is important for X chromosome inactivation, leading to healthy neural tube development. In short, the healthy development of neural tubes in female embryos needs the help of p53.”
X inactivation is an important process in all DNA-containing cells in the female body. Associate Professor Voss said the study confirmed a long-standing theory that women have additional risk factors for neural tube defects. Interruptions in the process of X chromosome inactivation may help explain why women are more likely to suffer from neural tube and other related birth defects than men.
“Women have two copies of X sex chromosomes, while men have only one. To keep women healthy, one of these X chromosomes must be inactivated in early developmental cells. If this inactivation does not occur effectively, the neural tube cannot be formed normally.
Previous studies have shown that p53 plays a role in normal neural tube development, but it is not clear how the cells of the double allele of the X chromosome gene affect the closure of the neural tube at the level of histomorphogenesis.
References
1. Lee, S. Y., Park, J. H., Jeong, S., Kim, B. Y., Kang, Y. K., Xu, Y., & Chung, S. K. (2019). K120R mutation inactivates p53 by creating an aberrant splice site leading to nonsense-mediated mRNA decay. Oncogene, 38(10), 1597.
2. Delbridge, A. R., Kueh, A. J., Ke, F., Zamudio, N. M., El-Saafin, F., Jansz, N., … & Hu, Y. (2019). Loss of p53 Causes Stochastic Aberrant X-Chromosome Inactivation and Female-Specific Neural Tube Defects. Cell reports, 27(2), 442-454.