Fish fins and human fingers are formed by similar mechanisms.

A team of researchers from the Superior Council for Scientific Research (CSIC) reveals that the mechanisms that use cells The fins of fish and the fingers of mammals to split are very similar, although these structures are very different. The results, obtained through experimentation on animal models such as medaka fish and mice, are published in the magazine. PNAS.

The mechanisms that fish fin cells and mammalian finger cells use to divide are very similar, despite being very different structures.

“A central and fascinating problem in evolutionary biology is trying to understand how a certain lineage of fish managed to conquer the terrestrial environment more than 350 million years ago”, he explains. Javier López-Ríos, CSIC Researcher at the Andalusian Center for Developmental Biology (CABD) “These first tetrapods (from the Greek tetra ‘four’ and podo ‘feet’) constitute the ancestors of all amphibians, reptiles, birds and mammals today, including humans”, adds the expert.

Among other changes, these animals developed lungs that allowed them to extract oxygen from the air and their fins, adapted for swimming, were transformed into robust legs that allowed them to walk in the terrestrial environment. “This limb structure (arm, forearm, wrist and fingers) is the same one we can see in the human skeleton. But where do these bones come from, which are not present in fish? ”, asks López-Ríos.

Number of fingers and the Gli3 gene

“Specifically, the number of fingers produced is under the control of the Shh-Gli3 pathway. If your activity decreases, less than five fingers are formed and if the path is more active, more are formed. In fact, the Gli3 gene is responsible for restricting the number of fingers to five, and mutations in humans or mice that inactivate this gene give rise to hands and feet with 6 to 9 fingers, which is known as polydactyly”, he says. the investigator.

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The study, whose first signatories are Joaquin Letelier and Silvia Naranjo, was the result of a collaboration between groups led by José Luis Gómez-Skarmeta (died in 2020), Juan Ramón Martínez-Morales and Javier López-Ríos, CABD researchers, CSIC joint institute, Pablo de Olavide University (UPO) and the Andalusia Council. In addition, it had the collaboration of the main university, in Santiago (Chile) and the prestigious paleontologist Neil Shubin, gives University of Chicago (USA).

These scientists asked themselves: what happens if we turn off the Gli3 gene in fish, which don’t have fingers?

To answer this question, López-Ríos explains: “We use technology CRISPR / Cas9 to eliminate the function of the Gli3 gene in the medaka fish, a fish of Japanese origin and evolutionarily separated from tetrapods by more than 400 million years of evolution. Surprisingly, fish without Gli3 activity develop much larger fins with much more bone, reminiscent of the polydactyly that occurs in mice and humans when Gli3 is not functioning properly. “

The number of fingers produced is under the control of the Shh-Gli3 pathway. If your activity decreases, fewer than five fingers are formed and if the path is more active, more are formed.

Javier López-Ríos

Similar but not identical mechanisms

“Using molecular and genetic methods, we were able to conclude that fish fins and our fingers are formed by similar but not identical mechanisms, and that new genes have been incorporated into these regulatory networks that control limb development to give rise to the skeleton of our arms and legs as we know them today”, highlights the specialist.

These studies reveal that the primary function of the Shh-Gli3 pathway was control fin size, and that this function was maintained in fish fins and tetrapod fingers, which indicates that, contrary to popular belief, there is a very deep ancestral relationship between these structures.

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