In mammals, hair follicles emerge during embryonic development, forming geometric patterns that vary from one species to another. But how is the position of each hair determined? A team from the University of Geneva (UNIGE) has shown that a simple mechanism based on the movement of cells in response to chemical signals can reproduce the formation of hair follicles in two mammalian species. Published in PNAS, the study sheds new light on the self-organizing principles that give rise to complex biological structures.

Hair, feathers, and most scales all develop from embryonic structures known as placodes. For decades, biologists have sought to understand how these placodes arrange themselves into the characteristic patterns observed in different species.

Until now, the prevailing explanation for laboratory mice (Mus musculus) was the so-called expansion-induction model. According to this theory, each newly formed placode produces an inhibitory molecule that prevents nearby placodes from forming. As embryonic skin expands, regions eventually move beyond the reach of this inhibitor, allowing new placodes to appear and progressively fill the gaps between existing ones. Although widely accepted, this model has never been experimentally demonstrated to apply more generally.

A simpler and more universal mechanism

The research group co-led by Athanasia Tzika, Senior Lecturer, and Michel Milinkovitch, Professor in the Department of Genetics and Evolution at UNIGE's Faculty of Science, investigated an alternative explanation based on chemotaxis – the ability of cells to migrate in response to chemical gradients. This mechanism, for example, directs white blood cells toward sites of inflammation.

Using a mathematical model describing interactions between mobile dermal cells and an attractive chemical signal produced by the epidermis, the researchers simulated embryonic skin growth and the progressive formation of placodes. Their results show that this self-organizing mechanism reproduces the same developmental dynamics previously attributed to the expansion–induction model in laboratory mice.

"Our findings show that the observed patterns do not require a complex system telling each placode where to form," explain Muhamet Ibrahimi and Ebrahim Jahanbakhsh, researchers in the Department of Genetics and Evolution. "Instead, placodes emerge spontaneously from local interactions between cells and chemical signals."

Two species, two architectures, one underlying principle

The team then tested the model in another rodent species, the spiny mouse (Acomys dimidiatus), whose coat displays a remarkably regular and highly oriented arrangement of hair follicles – a pattern that the classical expansion-induction model cannot explain.

By incorporating experimental data from three-dimensional imaging of embryonic skin, the researchers demonstrated that the very same chemotactic mechanism found in laboratory mice, combined with the spiny mouse's specific biochemical properties and skin growth characteristics, accurately reproduces its distinctive follicle organization.

"Our work suggests that simple cellular interactions can generate the remarkable diversity of tissue architectures observed throughout evolution," concludes Athanasia Tzika. "The differences observed between species therefore result from the same self-organization process, but with variations in the interactions between cells and chemical signals."