Long-Held Genetic Theory Doesn’t Quite Make the Grade, Biologists Find

NYU biologists have discovered new mechanisms that control how proteins are expressed in different regions of embryos, while also shedding additional insight into how physical traits are arranged in body plans. Their findings, which appeared in the journal Cell, call for reconsideration of a decades-old biological theory.

The researchers investigated morphogen theory, which posits that proteins controlling traits are arranged as gradients, with different amounts of proteins activating genes to create specified physical features. This theory has been used to explain why a tiger has stripes, among other phenomena.

The NYU biologists explored this process by studying the fruit fly Drosophila. They focused on one protein, Bicoid (Bcd), which is expressed in a gradient with the highest levels at the end of the embryo that will become the mature fly’s head.

The researchers, headed by Stephen Small, chair of NYU’s Department of Biology, examined a large number of target genes that are directly activated by Bcd. Each target gene is expressed in a region of the embryo with a boundary that corresponds to a specific structure.

By examining DNA sequences associated with these target genes, they discovered binding sites for three other proteins—Runt, Capicua, and Kruppel—which all act as repressors. All three proteins are expressed in gradients with the highest levels in the middle part of the embryo, and thus are positioned in exactly the opposite orientation compared to the Bcd activation gradient.

By changing the spatial distribution of the repressors and by manipulating their binding sites, Small and his colleagues showed that, contrary to morphogen theory, a single gradient of proteins does not have sufficient power to form the same body plan in each member of a species; however, if there are multiple gradients that work against each other, then the system becomes robust enough for normal development.

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