Discovery of a genetic dimmer switch controlling the embryonic development

A team of scientists from MRC Laboratory of Medical Sciences (LMS) has discovered a previously unknown mechanism that controls the way the “ON” and “off” gene switching genes during embryonic development. Published today in the developmental cell, their study sheds light on how various types of cells are produced in developing embryos.

The research was conducted by dr Irène Amblard and Dr. Vicki Metzis from the Development and Transcription Control Group, in cooperation with LMS facilities as well as chromatin and development, as well as computing groups of regulatory genomics.

All cells contain the same DNA, but they need to change specific “On” and “Off” genes – a process known as gene expression – to create different body parts. The cells in your eyes and shoulders contain the same genes, but “express” them differently to become part of the body. The work focused on the CDX2 gene. The duration of CDX2 expression helps to determine where and when the cell produces spinal cord progenitors. Scientists wanted to understand what processes control this short window.

The band discovered the DNA element, which they called “suppression”, which reduces the expression of genes in a way specific to the type and cells-in contrast to amplifiers or suppressors, other types of DNA elements that generally turn on or disable genes. By changing this element, they could tune as long or how strongly CDX2 was expressed, effectively acting like a “genetic dimmer switch”. The disruption of the “switch” in mouse embryos also confirmed its important role in shaping the developing body plan.

This groundbreaking trains to the programmable gene expression, offering the ability to precisely control gene activity in space and time. Discoveries not only deepen our understanding of developmental biology, but can inform new therapeutic strategies focused on non -coding genome. One day such approaches can enable treatment that selectively adapt the expression of genes in specific tissues, with implications for diseases caused by improper gene regulation.

Vicki emphasized the potential: “We are excited, because earlier studies suggest that our genome may contain many different types of elements that finely tune the expression of genes, but they were not easy to identify. If we can solve this challenge, this has a great potential for unlocking new ways of treating diseases by refining the expression of genes, where and when it is necessary.”

The study, financed by Wellcome, with the support of Medical Research Council, increases the growing work, examining how non-coding DNA regulates the regulation of genes-szar with deep implications for medicine, from designing new gene therapies to improvement of treatment.