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News

Control mechanism for biological pattern formation decoded

Max Planck Society : 23 April, 2007  (Technical Article)
A team of researchers in Freiburg have revealed the molecular mechanism which regulates pattern formation in the spacing and density of hair follicles. How are simple embryonic structures able to produce the varied and complex manifestations of living nature? Scientists in Freiburg have now identified proteins which regulate the pattern of hair formation in mice.
They have found that proteins produced by the skin, WNTs, which are essential for the induction of hair follicles, together with so-called DKK inhibitors control the spacing of the follicles. Using a mathematical model based on protein reactions and diffusions, researchers have been able to explain the dynamics and parameters of hair formation and to provide for the first time experimental confirmation of the Turing hypothesis of biological pattern formation.

As skin matures, a well-ordered sequence of molecular processes leads to the creation of different epidermal structures including the hair follicles of mammals and the feather follicles of birds. A particular feature of these follicles is their characteristic special distribution and density. Signal molecules from the WNT family play a dominant role among the substances which are involved in the induction and maturation of the follicles. Should these proteins not fulfil their function, then there are no morphological or molecular indications of pattern formation at all. The effect of WNTs is regulated by inhibitors from the DKK family of proteins, among others. These are also produced during follicle induction.

A possible explanation for the creation of biological patterns was offered during the 1950s by the English mathematician Alan Turing, who is also known for his participation in decoding the German Enigma code during WWII and his fundamental work on computer theory. Based on purely theoretical considerations, Turing proposed a reaction and diffusion mechanism between two chemical substances. Using mathematics, he proved that such a simple system could produce a multitude of patterns. If one substance, the activator, produces itself and an inhibitor, while the inhibitor breaks down or inhibits the activator, a spontaneous distribution pattern of substances in the form of stripes and patches can be created. An essential requirement for this is that the inhibitor can be distributed faster through diffusion than the activator, thereby stabilizing the irregular distribution. This kind of dynamic could determine the arrangement of periodic body structures and the pattern of fur markings.

Biologists from the Max Planck Institute of Immunobiology in Freiburg, in collaboration with theoretical physicists and mathematicians at the University of Freiburg, have for the first time supplied experimental proof of the Turing hypothesis of pattern formation. They succeeded in identifying substances which determine the distribution of hair follicles in mice. Taking a system biological approach, which linked experimental results with mathematical models and computer simulations, they were able to show that proteins in the WNT and DKK family play a crucial role in controlling the spatial arrangement of hair follicles and satisfy the theoretical requirements of the Turing hypothesis of pattern formation. In accordance with the predictions of the mathematical model, the density and arrangement of the hair follicles change with increased or reduced expression of the WNT and DKK proteins.

As well as the fundamental significance for understanding biological pattern formation, these findings form the basis for explaining in detail the process of hair formation, taking into account other factors which presumably work by controlling the WNTs and DKKs. As far as the general role of WNT signals in the creation of epidermal structures is concerned, the current study could be of long-term significance for the in vitro production of skin suitable for transplants.
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