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Mechanism of pigment pattern formation

In this project, we aim to elucidate the principle of skin pattern formation. There are various kinds of skin patterns. But do you know that there is a mathematical expression that automatically generates most of them?


The theory is called the reaction-diffusion model presented by Turing in 1952. Turing predicted that there is a possibility of generating waves (equally spaced patterns) in the field when the chemical reactions are combined well.


The idea of "waves in the skin" is strange. So,  biologists did not believe the hypothesis of Turing for long years. However, with the experiments we have done so far, many researchers are now recognizing that Turing's hypothesis was true.


We are proceeding with this research in the following order.

① Find dynamic properties of animal skin patterns that can be predicted by Turing's theory

② Identify cell-cell interactions that create Turing waves

③ Identify the molecular mechanisms underlying the interaction

① and ② have almost ended, and we are currently conducting research on ③.






A reaction-diffusion wave on the skin of the marine angelfish PomacanthusKondo S, Arai RNature 1995;376, 765 - 768


This paper proved for the first time that the striped pattern of fish has a dynamic property (moving) that is identical to the Turing wave. The research of our laboratory began from here.


Pattern regulation in the stripe of zebrafish suggests an underlying dynamic and autonomous mechanism.
Yamaguchi M, Yoshimoto E, Kondo S.
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4790-3. Epub 2007 Mar 12.​

The zebrafish pattern also moves according to the prediction of Turing's simulation. This means that we can elucidate the molecular mechanism of Turing pattern formation using this model animal.


Interactions between zebrafish pigment cells responsible for the generation of Turing patterns.
Nakamasu A, Takahashi G, Kanbe A, Kondo S.
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8429-34. 


The pattern is made by the interaction between two kinds of pigment cells. We can estimate the interaction between pigment cells by eliminating some pigment cells using laser and investigating how surrounding pigment cells affect the regeneration.


Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement.
Iwashita M, Watanabe M, Ishii M, Chen T, Johnson SL, Kurachi Y, Okada N, Kondo S.
PLoS Genet. 2006 Nov 24;2(11):e197.


Spot pattern of leopard Danio is caused by the mutation in the zebrafish connexin41.8 gene.
Watanabe M, Iwashita M, Ishii M, Kurachi Y, Kawakami A, Kondo S, Okada N.
EMBO Rep. 2006 Sep;7(9):893-7. Epub 2006 Jul 14.


I cloned two genes that cause altered pattern. From here, molecular level analysis begins.


Pigment pattern formation by contact-dependent depolarization.
Inaba M, Yamanaka H, Kondo S.
Science. 2012 Feb 10;335(6069):677.


we succeeded in the in vitro imaging of the interaction between the pigment cells


Involvement of Delta/Notch signaling in zebrafish adult pigment stripe patterning.
Hamada H, Watanabe M, Lau HE, Nishida T, Hasegawa T, Parichy DM, Kondo S.
Development. 2014 Jan;141(2):318-24.


We discovered that the interaction between pigment cells occurs not by diffusion of molecules but by direct stimulation of cellular processes. There are two types of protrusions, and it turned out that it mimics the diffusion effect of the reaction-diffusion principle.


Changing clothes easily: connexin41.8 regulates skin pattern variation.
Watanabe M, Kondo S.
Pigment Cell Melanoma Res. 2012 Feb 7. doi: 10.1111/j.1755-148X.2012.00984.x.

The CX418 gene that code a gap junction protein is responsible to the leopard mutation. By gradually changing the activity of this gene, every pattern that exists on the animal's skin was formed in zebrafish skin.


usui paper.png

The minimal gap-junction network among melanophores and xanthophores required for stripe pattern formation in zebrafish

Yuu Usui, Toshihiro Aramaki, Shigeru Kondo, Masakatsu Watanabe

Development 2019 146


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