How the dog, cow and ferret make their noses

The noses of many mammals, such as dogs, ferrets and cows, exhibit grooves forming a multitude of polygons bordered by creases that collect fluids and keep the nose wet. In a new publication published last week in Current Biology, Michel Milinkovitch's group analyzes in detail how these patterns form in the embryo using 3D imaging techniques and computer simulations. The group shows that differential growth of the skin tissue layers leads to the formation of domes, which are mechanically supported by the underlying blood vessels. This morphogenetic process, that they call ‘mechanical positional information’, described here for the first time, could help explain the formation of other biological structures associated with blood vessels.

The living world is full of remarkable shapes, some of which can be identified by their patterns of coloration or 3D motifs. Zebras and cheetahs, for example, can be recognized by their skin stripes or spots, while pine cones are characterized by their spiral organisation. These fascinating patterns are generated by various morphogenetic processes, i.e., the generation of shapes during embryonic development.

On the one hand, chemical self-organisational morphogenesis can be mediated by chemical reactions, as described by Alan Turing’s reaction-diffusion model, where chemical substances diffuse and interact to create relatively regular patterns, such as stripes, labyrinths or spots on the skin of many animals including fishes, reptiles and mammals. On the other hand, some shapes are the result of mechanical constraints. The human brain’s convolutions, for example, are produced by a process of differential growth: the cortex forms folds because it grows faster than the deeper layer to which it is attached.

At the LANE, Milinkovitch's team investigates the evolution of the developmental mechanisms producing the complexity and diversity of life. Their latest study focuses on the nose of dogs, ferrets and cows, which exhibit a singular network of polygonal structures. Indeed, the skin of the rhinarium (naked nose) of many mammalian species features a network of polygons formed by grooves in the skin. By retaining moisture, these grooves keep the nose wet and, among other functions, facilitate thermoregulation (by evaporative cooling as in elephants) and the collection of pheromones and odorant molecules.

First, the team collaborated with Aurélien Capitan and Hélène Jammes (Université Paris-Saclay, France), Karine Reynaud (École Nationale Vétérinaire d’Alfort, France) as well as Camino De Juan Romero and Victor Borrell (Institute of Neurosciences de San Juan de Alicante, Spain) for the very important and complex task of collecting embryonic series of dogs, cows and ferrets.

Second, researchers performed volumetric imaging of whole-mount rhinaria from sequences of embryonic and juvenile cows, dogs and ferrets. They demonstrated that rhinarial polygonal domains are not placode-derived skin appendages but arise through a self-organized mechanical process consisting of the constrained growth and buckling of the epidermal basal layer, followed by the formation of sharp epidermal creases exactly facing an underlying network of stiff blood vessels.

Third, our numerical simulations show that the mechanical stress generated by excessive epidermal growth concentrates at the positions of vessels that form rigid base points, causing the epidermal layers to move outwards and shape domes — akin to arches rising against stiff pillars. Remarkably, this gives rise to a larger length scale (the distance between the vessels) in the surface folding pattern than would otherwise occur in the absence of vessels.

These results hint at a concept of ‘mechanical positional information’ by which material properties of anatomical elements can impose local contraints to an otherwise globally self-organized mechanical pattern. In addition, the analyses of the rhinarial patterns in cow clones highlight a substantial level of stochasticity of the pre-pattern of vessels, while the numerical simulations also recapitulate the disruption of the folding pattern in cows affected by a hereditary disorder that causes hyperextensibility of the skin.

Much additional information is available in the original article:

Mechanical positional information guides the self-organized development of a polygonal network of creases in the skin of mammalian noses
Dagenais, Jahanbakhsh, Capitan, Jammes, Reynaud, De Juan Romero, Borrell & Milinkovitch
Current Biology 2024
DOI: 10.1016/j.cub.2024.09.055