MAY 17, 2019 3:59 PM PDT

Understanding Why Some Birth Defects are More Common in Girls

WRITTEN BY: Carmen Leitch

The p53 gene stops tumors from forming. Now researchers have found that the tumor-suppressing gene also has a critical role in the formation of the neural tube in female embryos. The neural tube is essential for embryonic development; the brain and spinal cord are formed from it. When the neural tube fails to close, birth defects like spina bifida can occur. Female infants are far more likely to be born with spina bifida than males, and this work, which has been published in Cell Reports, can explain why. 

The p53 gene plays a vital role in a process called X chromosome inactivation. Human gender is determined by the sex chromosomes. The X chromosome contains genes necessary for development, while the Y chromosome only carries genes for male development. Females have two X chromosomes, and men have an X chromosome and a Y chromosome. With two X chromosomes, women have two copies of some of the genes that are necessary for human development, and extra copies of genes can cause errors. Therefore, the extra X chromosome has to be inactivated so it won’t cause interference. Every cell turns off one of the X chromosomes it carries in the genome at random, to ensure normal growth.

"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," said Associate Professor Anne Voss of the Walter and Eliza Hall Institute of Medical Research (WEHI).

This study, said Voss, has confirmed what scientists have long thought; there is an additional factor influencing the risk of neural tube defects in females. A failure in the X-inactivation process can help explain this extra risk.

The long non-coding RNA called Xist helps carry out X-inactivation. Mice that lack Xist don’t survive through embryonic development and die before birth with an open neural tube. In this study, the researchers used a mouse model to show that when the p53 gene was lost, Xist levels are lower than they should be, and female mice display a range of neural tube defects at birth. The work, said the researchers, can help show how p53 influences genes that are required for normal development.

"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," said Professor Andreas Strasser of WEHI.


Sources: AAAS/Eurekalert! via Walter and Eliza Hall Institute, Cell Reports

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 01, 2021
Genetics & Genomics
Genetic Connnections to Osteoerthritis
NOV 01, 2021
Genetic Connnections to Osteoerthritis
Osteoarthritis is a painful condition in which joints become inflamed, leading them to feel stiff or sore, especially in ...
NOV 11, 2021
Health & Medicine
The Taconic-Cyagen Academic Model Generation Alliance
NOV 11, 2021
The Taconic-Cyagen Academic Model Generation Alliance
With more than 15 years of experience in genetic engineering, Cyagen utilizes a highly efficient process, including prop ...
NOV 09, 2021
Health & Medicine
How to Search the Cyagen Knockout Catalog Models Resource?
NOV 09, 2021
How to Search the Cyagen Knockout Catalog Models Resource?
The Cyagen Knockout Catalog Models repository provides researchers in the Americas and Europe with ready-to-use knockout ...
NOV 04, 2021
Microbiology
Investigating the Gut Virome
NOV 04, 2021
Investigating the Gut Virome
The gut microbiome is a critical part of human health. Research has shown that many types of bacteria may reside there. ...
NOV 23, 2021
Clinical & Molecular DX
Scientists Enter Uncharted Territory of the Cancer Genome, Emerge Victorious
NOV 23, 2021
Scientists Enter Uncharted Territory of the Cancer Genome, Emerge Victorious
Cancer is a genetic disease—it stems from specific changes in the DNA sequences of the cancer cell genome. Over th ...
NOV 22, 2021
Genetics & Genomics
Revealing the Battle Between Organisms & Selfish Genetic Elements
NOV 22, 2021
Revealing the Battle Between Organisms & Selfish Genetic Elements
Evolution has allowed organisms to adapt to their environments, sometimes in very specific ways, through changes in thei ...
Loading Comments...