New York, NY, USA. New mechanisms that control protein expression in different regions of embryos shed additional insight into how physical traits are arranged in body plans.

The findings, which appear in the journal Cell, call for reconsideration of morphogen theory, which posits that proteins controlling traits are arranged as gradients, with different amounts of proteins activating genes to create specified physical features.


Morphogen Theory contends that physical features are necessarily tied to absolute concentrations of proteins within the morphogen gradient. A morphogenic substance oversses tissue development and the correct positioning of specialized cell types within a tissue. Under the theory, if a certain critical mass of protein is present, then a given physical feature — for example, cells that make the skin on your forehead — will appear. If less than that critical mass is present, a different structure — say, the skin that makes your eyebrows — will appear, and a boundary will be formed between the two structures.



Alan Turing (23 June 1912 – 7 June 1954), the mathematician and code breaker, first proposed morphogen theory in the 1950s. Refined in the 1960s by Lewis Wolpert, the theory has been used to explain why a tiger has stripes, among other phenomena.

The current research does raise questions about the theory, but the NYU bologists say their findings did not falsify it, but rather suggest morphogen theory needs some additional refinement.But some biologists have raised questions, offering alternative views suggesting that physical features are not necessarily the result of a specified number of proteins, but, rather, come from more complex interactions between multiple gradients that work against one another.

Biologists from New York University (NYU) explored this process by studying the fruit fly Drosophila, a powerful model for studying genetic development as it is amenable to precise genetic manipulations. They focused on one protein, Bicoid (Bcd), which is expressed in a gradient with 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, the NYU researchers discovered binding sites for three other proteins — Runt, Capicua, and Kruppel — which all act as repressors. All three proteins are expressed in gradients with 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 these repressors antagonize Bcd-dependent activation and are absolutely critical for establishing the correct order of boundaries that are found in a normal embryo.

In other words, contrary to Turing's 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.