A team of scientists in the MRC Laboratory of Medical Sciences (LMS) has revealed a previous unknown mechanism that controls the way genes are activated ‘and’ off ‘during fetal development. Published today in the development cell, their study illuminates how different types of cells are produced in the development of embryos.
The investigation was conducted by Dr. Irène Amblard and Dr. Vicki Metzis from the Development and Transcriptional Team, in collaboration with the LMS facilities and chromatin and development groups and computing regulators.
All cells contain the same DNA, but they must convert specific genes’ and ‘off’ – a process known as a gene expression – to create different parts of the body. The cells in your eyes and hands host the same genes, but “express” them differently to become every part of the body. The project focused on the CDX2 gene. The duration of CDX2 expression helps to determine where and when a cell produces ancestral spinal cord. The researchers wanted to understand what procedures they control this short window.
The group discovered a DNA element that characterized a “weakener”, which reduces gene expression in a manner and specific cell type-as opposed to amplifiers or silencers, other types of DNA elements that activate or disable genes. By changing this element, they could coordinate how long or how strongly the CDX2 was expressed, effectively acting as a “Dimmer genetic switch”. The “switch” disorder in mouse embryos also confirmed its essential role in shaping the developing body.
This discovery paves the way to the programmable gene expression, offering the ability to accurately control the activity of genes in space and time. The findings not only deepen our understanding of development biology, but can update new therapeutic strategies aimed at the non -coding genome. Such approaches could one day allow treatments that selectively adapt gene expression to specific tissues, with effects on diseases caused by incorrect gene regulation.
Vicki emphasized the potential: “We are excited because previous research suggests that our genome can accommodate many different types of elements that coordinate gene expression, but it was not easy to identify. If we can face this challenge, it has a new challenge, when necessary ”.
The study, funded by Wellcome, with support from the Medical Research Council, adds to an increasing work body that explores how non-coding DNA governs the regulation of genes-a deep impact on medicine, from the design of new gene therapies to improve therapies.
Source:
Magazine report:
Amblard, I., et al. (2025). A dual amplifier element ensures transient CDX2 expression during the formation of the posterior body of the mouse. Growth cell. doi.org/10.1016/j.devcel.2025.06.006.
