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April 24, 2023

In double pack – paired proteins give you wings

For hands, feet or wings to develop the correct shape and size, harmonious interaction of a complex orchestra of proteins is essential. The research team led by Prof. Markus Affolter at the Biozentrum, University of Basel, has now discovered that two proteins form a closely connected duo in this interplay. Only together they ensure the proper development of the fruit fly wing.

Two proteins together ensure the correct development of the fruit fly wing.

From fingers on our hands to the wings of insects, the bodies of different animals form limbs of various shapes and sizes. Morphogens are signaling molecules that provide the necessary information for the proper development of limbs, ensuring consistent size and shape of hands or wings. 

For many years, Prof. Markus Affolter’s team at the Biozentrum, University of Basel, has been investigating how the morphogen Dpp controls wing growth in the fruit fly Drosophila melanogaster. In their current study, published in the journal “Developmental Cell”, the scientists demonstrate that Dpp does not work alone, but tightly associated in a double pack with another morphogen.

Morphogens in duet
Using synthetic receptors, the team discovered that the morphogen Gbb is directly involved in giving the wing its correct pattern and shape. The two proteins Dpp and Gbb are not simply present next to each other in the tissue, but form covalently linked heterodimers. “By targeted gene editing and protein manipulation, we were able to trace the two morphogens in the tissue and show that Dpp and Gbb are always physically linked in the developing wing”, explains Gustavo Aguilar, one of the first authors of the study. “A disruption of this connection results in wing patterning defects.”  

Analogous concentration gradients
In addition, the researchers were able to demonstrate that both morphogens, Dpp and Gbb, form in unison a concentration gradient in the tissue. While they are present in high concentration in the center, at the source of growth, the concentration in the periphery of the wing is low. This gradient plays a key role in wing development.

Also in humans, a large number of morphogens control the development of organs and limbs. “It is essential that the morphogens interact properly and are orchestrated correctly”, adds Markus Affolter. If morphogens are not produced in sufficient quantities, this can lead to malformations. "How the development of the wing is controlled also provides insight about how our organs and limbs are formed."

Original publication:
Milena Bauer, Gustavo Aguilar, Kristi A. Wharton, Shinya Matsuda, Markus Affolter: Heterodimerization-dependent secretion of Bone Morphogenetic Proteins in Drosophila. Developmental Cell. Published online 24 April 2023.

Contact: Katrin Bühler and Heike Sacher, Communications Biozentrum