Of patches, blotches, speckles and stripes


From flags to fashion, people love patterns of colors and shapes and use them to convey meaning. Nature is also replete with colorful patterns and employs them to send signals, but how are such patterns generated without our doing? By information or self-organization? John Maynard Smith pointedly asks in his book entitled ‘Shaping Life’. A good question, as the debate has not yet been entirely settled. Proponents of self-organization believe that most if not all repetitive coat patterns can be explained by mathematical models originally based on the reaction-diffusion mechanism proposed by Turing in 1952. Suppose a factor exists in the skin that causes melanocytes to go black, induces an inhibitor that causes them to go white, and is not precisely at equal concentrations at every point on a body surface. Suppose also that the inhibitor diffuses faster than the activator and needs to act before the activator steps in, and – bingo!– there will be black spots surrounded by white areas. One need only tinker with the parameters of an otherwise common algorithm to generate virtually every pattern in nature on a computer screen. Conceptually, then, genes would set the parameters (body size, concentrations, diffusion rates, etc.) and patterns would inevitably and logically emerge. But then there are those who hold that this view underplays the importance of genetic programming, which, after all, underlies all adaptive evolution. They would argue that the pigment cell is not just pushed around by extrinsic factors but is actively engaged in the communication with the local environment and uses its own color genes to draw patterns. As is often the case in such debates, the truth may lie somewhere in between. There is evidence suggesting that patterning genes conceivably influencing reaction-diffusion processes in the integument may have appeared early in evolution and been preserved, and that pigmentation genes interpreting these pattern genes may have evolved later and independently on multiple occasions. This and other questions concerning pigment patterns are discussed in this issue in the commentary by Kaelin and Barsh on the genetics of pigmentation in the cat, by Walker and Gunn in a review on pigment type switching, and by myself in a News and Views piece on sex-specific coloration in fish. Hellström and colleagues from Leif Anderson’s group in Uppsala, Sweden, investigate the genetics of sex-linked barring in chickens and find, intriguingly, that the cell cycle and tumor suppressor gene CDKN2A is involved. Harris and colleagues from the Pavan laboratory at NIH in the US review the various roles SOX proteins play in the development of pigmentation and its regulation in the adult, and they also discuss the involvement of these transcription factors in malignant transformation.

Alas, this brings us to pathology, the flip side of all the joy we get from the beauty in animal coloration. In fact, PCMR devotes a substantial number of pages to pathology, for the analysis and treatment of hypo- and hyperpigmentations or pigment cell-associated malignancies. There are several papers in this issue that deal with one or the other factor that is dysregulated in melanoma. Ryan and colleagues, for instance, use comparative genome hybridization to show that the gene encoding Topoisomerase-1 is amplified in aggressive melanoma, giving a poor prognosis. Wang and colleagues show that poor melanoma prognosis is also predicted by aberrant expression of alpha-1 antichymotrypsin. Chen and colleagues show increased expression of Cullin1, which is part of a large ubiquitin E3 ligase complex, in early stage melanoma. VanBrocklin and colleagues use a promising system in mice that makes it possible to evaluate the role of individual genes in melanoma formation alone and in combination. Needless to say, there are many more interesting papers in this issue that should be highlighted, and I encourage you, the reader, to leaf through the pages and mark (and cite!) all the compelling studies that pique your interest.