One of the longest-standing questions in biology is how a living thing that starts out as a blob of cells transforms into an organisms with different types of tissues. The answer would explain how a zebra gets its stripes and how a leopard gets its spots. An elegant model based on chemical signaling proposed by Alan Turing has been the favored explanation for more than 50 years.

Turing's theory is only one part of the story. According to Amy Shyer, a developmental biologist at Rockefeller University, we have been blinded to how widely it should be used. Physical forces of contraction and compression that act on cells as they grow and divide could be a central role.

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She has evidence of it. In a paper published in Cell in May, Shyer, her co-senior author and fellow developmental Biologist Alan Rodriguez and their colleagues showed that mechanical forces could induce chicken skin to create follicles for growing feathers. As surface tension pulls water into spherical beads on a glass surface, so too can the physical tensions within an embryo set up patterns that guide growth and gene activity in developing tissues.

As an organisms grows and develops, the cells in its tissues pull and push on each other and on the supportiveprotein scaffolding to which they are intricately linked The formation of complicated patterns may be caused by the forces and changes in the pressure of the cells. No studies have been able to tease apart the effects of these physical forces on the stew.

Pulling Out a Pattern

In the laboratory of morphogenesis at Rockefeller University, the skin from a chicken embryo was removed and the tissue was destroyed to separate the cells. They put the cellular solution into a petri dish and let it grow. They watched as the skin cells formed a ring on the floor of the dish, like a ball of cells. The cells pulled on the fibers in the matrix. The fibers were bunched together and pushed apart over 48 hours.

Micrographs of cell organization in experiment at 8, 20 and 30 hours.

There are high-magnification views of the self- organizing cells. The cells get closer together because of the pulling force between them.

Brian Camley, a biophysicist who was not involved in the study, said that the setup was simple and that there was a beautiful pattern coming out.

The researchers showed that the pattern was affected by physical tension in the embryo. The most surprising thing was the way the cells interacted with the matrix in order to create patterns. It's a dance between the two.

Contractility could be enough to drive pattern formation. It is a new essential piece.

Mechanics First, Genes Later?

In 1917, the mathematician D'Arcy Wentworth Thompson proposed that physical forces might be involved. In his book On Growth and Form, Thompson talked about how the forces that govern horn and tooth formation are similar to those that govern drops of liquid.

Amy Shyer and Alan Rodrigues of Rockefeller University.

Thompson's ideas were overshadowed by Turing's explanation, which made sense to the emerging understanding of genes. Turing suggested in a 1952 paper that the patterns of spots, stripes and even the sculpted shapes of bones in the skeleton were the result of a swirl of chemicals that interacted with each other. The morphogens kick on genetic programs that cause fingers, rows of teeth or other parts to develop.

Turing's theory became a core part of developmental biology because it was easy to understand. Most mechanisms of biology have a strong view of genes.

Something wasn't found in that solution. Scientists should be able to show that one precedes the other if chemical morphogens drive development.

They couldn't show it in the lab. They took small slices of chicken embryo skin and watched as the tissue got closer to forming a follicle. They tracked the activity of the genes involved in follicle formation. The cells bunched up around the same time as the genes were being expressed.

It was like mechanics was generating these shapes instead of genes. They showed that removing some of the genes didn't disrupt the process. She said that something else might be going on here.

The Active Soft Matter of Biology

They hope that their work will help understand the role of physics and its interplay with chemicals and genes.

A researcher at the University of Chicago who was not involved in the study said that all of the genes, signaling and production of forces in cell movement are tied together.

The role of the matrix is more important than scientists realize, according to Munro. The forces in the matrix have been linked to fruit fly eggs.

The man agreed. The cells and the matrix are forming something. He thinks that this is a new way of thinking about the regulation of the development of the embryo. They hope to combine the physical forces in development with themolecular view in the future.

The answers to the important questions might not be at the level of the genomes if we just studied the genome with more depth and rigor. The decision-making can be happening outside of the cell through the physical interactions of cells with each other.

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