The embryo of the fruit fly Drosophila, here under a microscope during its transformation from egg into larva. Signalling molecules assign the correct role to each cell (here the white dots). | Image: Philipp Keller / Howard Hughes Medical Institute

The embryo has fascinated humans at least since Antiquity, but just how does a cluster of cells turn itself into a complex organism? One surprisingly accurate description was written in India several centuries before the modern era: “After seven nights, it is like a bubble, and in two weeks it becomes a ball”. It wasn’t until the second half of the 20th century, however, that scientists began to understand it at the cellular level.

In this pursuit, one pivotal discovery was morphogens. These molecules play a central role in the formation of the embryo. They signal to cells how to specialise: liver, bone, skin, or neuron; and to a large extent where to be situated. At the University of Basel, Markus Affolter studies a morphogen called ‘Dpp’ in the fruit fly. He has developed a method to inhibit some of its effects using nanoparticles, allowing him to improve our understanding of how it works.

A molecular score with no wrong notes

“The mechanism of Dpp is the same in vertebrates, including humans, in the form of the morphogen BMP-2, which is substitutable and practically identical to Dpp”, says Affolter. But the fruit fly remains the model of choice for studying the role of the molecule in the development of the embryo, especially because it only takes 10 days for a fertilised egg to become an adult.

Dpp was identified in the late 1980s and is now known to be involved in some extremely intricate mechanisms. Indeed, scientists are still a long way off understanding all of its secrets. It is discharged in specific places at specific times as the embryo forms, and it works in concert with other molecules. It’s a real musical score, where the slightest variation can lead to the playing of a wrong note, i.e., a birth defect.

A new method to study morphogens

Affolter is looking particularly at one Dpp parameter, which has a major impact on how it works: its local concentration. The quantity of Dpp decreases with distance from its secreting cells, which are grouped in specific locations. This leads to the creation of Dpp gradients. The further away a receptor cell is, the lower its exposure to Dpp. As the level of concentration determines which effect is caused, every cell – according to its location – receives the dose necessary to ensure the development of a normal embryo.

Thanks to their use of nanoparticles, Affolter and his colleagues have become the first to alter these gradients directly in a gestating fly embryo. One of the nanoparticles prevents the dispersion of Dpp – and hence the creation of a gradient – whereas another offsets its effect. By comparing the respective results, the team has shown the determining role played by Dpp concentration gradients in the development of the rear part of fruit fly wings, but much less – even not at all – of the front part.

“We have a new tool that allows us to modify the action of a molecule in a living organism”.Markus Affolter

“Until today, scientists working with fruit flies have mainly induced genetic mutations, first using X-rays, then more precisely using Crispr (Ed. molecular scissors)”, says Affolter. “Our use of nanoparticles has created a new tool, allowing us to modify the action of a molecule in a living organism directly in order to understand better the effect of morphogen gradients”.

The role of morphogens is not limited to developmental biology. They are secreted after embryogenesis, for example, to regenerate damaged tissue and to govern cellular proliferation. There is one called ‘Wingless’ that interacts with Dpp in the development of fruit fly wings. It has been linked to a series of human cancers, including colon, breast and skin cancers, and is now being examined in a series of experimental therapies. According to Affolter, this progress is all thanks to the humble fruit fly.

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