How the Zebrafish Gets its Stripes (or Spots)

Simulating how cells form patterns.

Normal zebrafish have stripes, but mutant forms may display spots, blotches, or labyrinthine patterns. It’s a scenario that Rudyard Kipling might turn into a wonderful “just-so” story. But a more scientific explanation comes from a new computer model that can replicate the diverse ways that pigmented cells organize themselves on zebrafish skin. The results may help scientists gain a better understanding of development in general, helping explain how myriads of cells turn into tissues, organs, and entire organisms.


“Our aim here is not to build better zebrafish,” says Troy Shinbrot, PhD, who developed the model along with his graduate student, Carlos Caicedo-Carvajal. “We want to understand how tissues and organs develop and how cells migrate, survive, and form the shapes that govern function.” The work was published in Developmental Biology in January 2008.


Normal and leo mutant zebrafish (left) and their corresponding normal and abnormal simulated patterns (right). Courtesy of Troy Shinbrot and David Parichy. Reprinted from Developmental Biology, 315, CaicedoCarvajal, CE; Shinbrot, T, In Silico Zebrafish Pattern Formation, 397–403 (2008), with permission from ElsevierAccording to Alan Turing’s theory from the 1950s, pigmented cells arrange themselves into patterns under the guidance of chemical agents. More recent studies of zebrafish stripe formation sug- gest that mechanical interactions between cells—how strongly they push or pull one another—could also play a vital role. To test the latter hypothesis, Shinbrot and Caicedo-Carvajal developed a simplified energy-minimization model of cells of two different colors interacting within a rectangular region.


Using different combinations of values for the forces between like (homotypic) and unlike (heterotypic) cells, the researchers generated a range of possible patterns. “To get stripes, we need both heterotypic attraction and a delicately balanced homotypic repulsion,” says Shinbrot. If these conditions were not met, the simulations showed that spotted, striated, labyrinthine, and other non-striped patterns developed; in particular, when all the inter-cellular forces were attractive, only spots formed. The researchers showed that some of these abnormal patterns resemble those observed on certain mutant zebrafish varieties with defective pigment pathways.


This in silico approach could be applied to a broad range of problems in cellular development, says Shinbrot. The researchers are now using it to help oncologists compare four different patterns of abnormal tissue commonly seen in early breast cancer tumors.


“The authors have done a nice job of showing how you can produce a whole repertoire of patterns simply by tuning the strengths of attractive and repulsive cell interactions,” says Ed Munro, PhD, a computational cell biologist at the University of Washington in Seattle. However, Munro cautions that the results obtained using the authors’ simplified model need further biological validation. “By demonstrating one way in which cells can make patterns, you haven’t shown that’s how embryos do it,” he notes.

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