How cells move to create patterns on a butterfly's wings

Washington, June 22 : Johns Hopkins researchers say that they have discovered a gene that underpins the process of cell movement to create patterns like a zebra's stripes, a seashell's spirals, a butterfly's wings, etc. Writing about their study in the journal Developmental Cell, the researchers said that their finding might be useful for scientists trying to gain a deeper understanding of how cancer cells move.

"Pattern formation is a classic problem in embryology. At some point, cells in an embryo must separate into those that will become heart cells, liver cells, blood cells and so on. Although this has been studied for years, there is still a lot we don't understand," said Dr. Denise Montell, a professor of biological chemistry.

The researchers studied the process of how about six cells in the fruit fly distinguish themselves from neighbouring cells and move from one location in the ovary to another during egg development.

"In order for this cell migration to happen, you have to have cells that go and cells that stay. There must be a clear distinction - a separation between different types of cells, which on the surface look the same," Montell said.

The researchers already knew that a specific signal is necessary for getting the fly egg cells to move.

They, however, were unsure how the signal creates clear lines for the pattern formation despite the fact that it travels in between surrounding cells, and gradually fades away while moving outwards, just like drops of ink spreading out on wet paper do.

Upon examining flies containing mutations in different genes, the researchers found that a gene called apontic is important for converting a graded signal into a clear move or stay signal.

"When apontic is mutated, the distinction between migrating and non-migrating cells is fuzzy. In these mutants, we see a lot of cases where migrating cells do not properly detach from their neighbours but instead drag them along as they move away," said Dr. Michelle Starz-Gaiano, a postdoctoral fellow in biological chemistry.

To find out how apontic works, the researchers collaborated with a mathematician at the Max Planck Institute in Germany named Hans Meinhardt, who designed a computer model that could simulate how graded signals are converted to commands that tell cells to move or to stay.

The research team built a simple circuit that can predict a cell's behaviour using the graded signal, apontic, and another previously discovered protein called slbo.

The computer model showed that the graded signal turned on both apontic and slbo in a cell, but both proteins worked against each other: when one gained a slight advantage, the other weakened, which in turn causes the first to gain an even bigger advantage.

That continued until one of the two proteins dominated in each cell.

The cell moved when slbo won, but the cell stayed put when apontic won. Thus, a clear separation between move or stay was achieved.

"Not only is this a new solution to the problem of how to create a pattern out of no pattern, but we have also discovered that apontic is a new regulator of cell migration," says Montell.

The researchers are of the opinion that cell migration might have a role in the spreading of cancer cells beyond an original tumour to other areas of the body, and that understanding and therefore being able to manipulate the cell migration pathway could potentially prevent the development of new tumours.

At this stage, Montell says, "it's more about just understanding what the positive and negative regulators of cell migration are."

ANI