Turing Pattern Fingered for Digit Formation

Born in 1912 in London, Alan Turing has been the subject of numerous centenary celebrations by scientists around the world this year. The mathematician, known as the father of computer science and artificial intelligence, is still prompting new discoveries more than 50 years after his death. On page 1476, a team of biologists offers fresh evidence that one of Turing's last theories guides how some parts of the body develop.

The new work concerns the mystery of how mammalian limbs get their standard five digits. The suite of genes that governs limb development includes some of the best-studied in the field, but explaining why a hand has five fingers— and why some mutations cause more or fewer to form—has left developmental biologists perplexed.

As more Hox genes are removed from a developing mouse limb lacking the geneGli3, more digits form, a pattern fitting a model developed by mathematician Alan Turing.

The answer may lie in a set of equations Turing developed. In 1952, 2 years before his untimely death, the man who helped break the German Enigma code during World War II published a paper on “The Chemical Basis of Morphogenesis” that described how two interacting chemicals diffusing through space could form interacting wave patterns that produce spots like a leopard's or stripes like a zebra's. The pattern depends on how fast the molecules diffuse, whether they activate or inhibit each other, and other factors—all parameters of Turing's equations.

The theory has long fascinated theoretical biologists, but it had found less support among those studying actual development. Recently, however, experiments have suggested that Turing mechanisms play a role in the growth of feathers, hair follicles, the branching pattern of lungs, and even the left-right asymmetry that puts the heart on the left side of the chest. Turing's model also appears to describe the pattern that leads to digit formation in the developing mouse paw, concludes the new study by developmental biologists Maria Ros of the University of Cantabria in Santander, Spain, and Marie Kmita of the Clinical Research Institute of Montreal in Canada; theoretical biologist James Sharpe of the European Molecular Biology Laboratory Centre for Genomic Regulation in Barcelona, Spain; and their colleagues. The work is a significant advance for Turing-type mechanisms in development, says Shigeru Kondo, a theoretical biologist at Nagoya University in Japan, especially because limb formation commands more respect among developmental biologists than pigment patterns or feather buds.

A widely accepted model of digit formation involves the diffusion of proteins and signaling molecules to form a relatively smooth gradient across the developing hand or paw. This gradient, some argue, contains enough information to tell a cell whether it should condense into cartilage and form the beginnings of a finger or toe or ultimately die back, forming the space between digits.

Ros and Kmita were exploring the process of digit formation by studying Hox genes. The subject of the 1995 Nobel Prize in physiology or medicine, the Hox family of genes famously helps control the head-to-tail patterning of embryos. Previous studies had shown that certain Hox genes interact with genes called Shh and Gli3 as the mouse paw is forming, and that knocking out either Shhor Gli3 causes extra digits to form—typically seven or eight. One theory was that removing those genes led to a higher-than-normal dose of the Hox genes, which then caused extra toes. Ros and Kmita thought eliminating the activity of some of the Hox genes could bring the digit number back down to five.

What they saw was the opposite. When they knocked out various Hox genes in addition to knocking out Gli3, the resulting mice had even more digits. And the more Hox genes they removed, the more digits formed. The most extreme mutants had 14 toes on their developing paws.

The researchers were surprised by another observation: As they took away more Hox genes, the number of digits increased, but the overall paw size remained relatively unchanged. Other experiments had suggested that additional digits resulted from more tissue. But the thinner and more densely packed digits suggested that losing Hox genes seemed to shorten the spacing between digits—the wavelength in Turing's mathematical language.

Theoreticians have suggested for decades that a Turing-type wave function might help pattern fingers and other digits, Sharpe says. But, he adds, the 14-toed mice and other Gli3/Hox knockouts are the first example of a genetic modulator of wavelength—one of the missing pieces of evidence that Turing's theory could be at work in hand development.

Several key pieces are still missing, however. Turing's model requires two diffusing and interacting molecules that form a pattern, andHox genes don't diffuse through tissue. Instead, Sharpe says, they must control other—still mysterious—factors that signal which cells start to form cartilage—and ultimately digits. “The Hox genes are known to be desperately important in limb development, but it has been almost impossible to name tangible roles for them,” he says. “In this phase of limb development, their role seems to be to regulate the Turing mechanism.”

A Turing “model fits quite well,” says Denis Duboule, a developmental biologist at the Swiss Federal Institute of Technology in Lausanne, though he says he'd like to see if an experiment that increases Hox genes results in the formation of fewer digits. “The next question is, how does it work?” Hox genes are transcription factors that turn other genes on and off, Duboule notes, so they influence multiple genetic pathways. “I must say, it's a very difficult question.”

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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.

There is nothing glorious about what our ancestors call history,
it is simply a succession of mistakes, intolerances and violations.

On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.

Rael
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วันศุกร์ที่ 21 ธันวาคม พ.ศ. 2555

[rael-science] Turing Pattern Fingered for Digit Formation‏

Turing Pattern Fingered for Digit Formation

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