New research has revealed how the famous tumor suppressor gene p53 is surprisingly critical for development of the neural tube in female embryos. This is important because healthy development of the neural tube is needed for the brain and the spinal cord to form properly.
The study, published in the journal Cell Reports, explained p53's involvement in a molecular process specific to females called 'X chromosome inactivation'. The new findings helped to clarify why females are significantly more likely than males to be born with neural tube birth defects, such as spina bifida.
The collaborative teams were surprised to discover how the gene p53, famous throughout scientific literature and history for its role in protecting us from cancer, also played a pivotal role in healthy neural tube development.
The research showed how p53 influenced the function of genes required for fostering the production of healthy neural tube cells in the female embryo. The female p53−/− embryonic neural tube samples showed fewer cells with inactive X chromosome markers Xist and H3K27me3 and a concomitant increase in biallelic expression of the X-linked genes, Huwe1 and Usp9x. Decreased Xist and increased X-linked gene expression was confirmed by RNA sequencing. Moreover, authors found that p53 directly bound response elements in the X chromosome inactivation center (XIC).
"Healthy development is a very precise and precariously balanced process. p53 helps with this balancing act in the female embryo by producing normal levels of Xist RNA, part of an intricate molecular process important for X chromosome inactivation. This in turn leads to healthy neural tube development. Simply put, healthy neural tube development in the female embryo requires the help of p53,"the senior author said.
Another author said the study confirmed a long-standing theory that females had an additional risk factor for neural tube defects and that a breakdown in the associated X chromosome inactivation process could help to explain why females were more likely than males to have neural tube-related birth defects.
"Females have two copies of the 'X' sex chromosome, while males only have one copy. In order to maintain health in females, one of these X chromosomes must be inactivated in cells early on during development. If this inactivation does not occur efficiently, the neural tube will not form properly. Previous research indicated that p53 played a role in normal neural tube development, but it had never been shown exactly how this worked until now," the author said.
How tumor repressor protects against neural tube defects
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