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University of Basel

29 September 2021

Robust gene networks from the depths of our evolutionary history

hand holding a fossil
A series of switches in the genome ensures the correct development of extremities - and gave evolution leeway to produce very different extremities. (Photo: KEYSTONE/Science Photo Library/Paul D Stewart)

A sophisticated system guides the development of our limbs. Researchers at University of Basel have shed new light on the genetic toolkit used during evolution to create a range of different extremities such as fins, wings, hooves, toes and fingers.

Much can go wrong when a fertilized egg develops into an embryo and ultimately gives rise to a newborn as mutations in the genome that affect development are relatively common. The fact that embryonic development is usually flawless for humans and animals is due to the fact that genetic programs are controlled by series of gene circuits that can back one another up in a self-regulatory fashion.

This robustness of developmental programs is a key interest of the research group led by Professor Rolf Zeller and PD. Dr. Aimée Zuniga at the Department of Biomedicine, University of Basel. They seek to gain insights into this process studying a key regulator of limb development, a protein called “Gremlin1”. This protein stops cells from forming bones too early and functions in fine tuning the activity of several signaling networks by connecting them with one another. Most importantly, Gremlin1 is responsible for the correct formation of the so called limb buds, which are the tiny embryonic structure that will give rise to our extremities.

A network secures perfect development

Studies using mouse embryos have enabled researchers to decipher yet another level of regulation - and robustness - of this developmental program. In the scientific journal Nature Communications, they describe a series of “switches” embedded in the genome of all vertebrates which ensures that the correct amount of Gremlin1 is produced at the right place. These switches are called “enhancers”.

Zuniga compares the system that she and her team are investigating with a room’s lighting system that is controlled by a series of switches. The light enables one to read the instructions to build correctly formed extremities. “In the beginning, we did not know what each individual switch contributes to lighting the room,” the researcher explains. “There could be a master switch that turns off all lights, making the instructions impossible to read. Instead, we now know that all switches contribute to the lighting system: if one switch is broken the amount of light is only marginally or not at all affected and the information can still be read. This is why the system is so robust. On the other hand, once too many switches are broken, too little of the information can be read, and in the worst case none at all.”

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