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How Did You Get Five Fingers?

Your arms and toes began as tiny buds that sprouted from your sides when you were just a four-week-old embryo (胚胎). By six weeks, these limb buds had grown longer and five rods of cartilage 软骨) had appeared in their flattened tips. By week seven, the cells between the rods had died away, forming five small fingers or toes from once-solid masses of flesh.

Now, a team of scientists led by James Sharpe from the Centre for Genomic Regulation in Barcelona has discovered that these events are carefully orchestrated by three molecules. They mark out zones in the embryonic hand where fingers will grow, and the spaces in between that are destined to die. Without such molecules, pianos and keyboards wouldn’t exist, and jazz hands would be jazz palms.

These three molecules work in a way first envisioned by Alan Turing, a legendary English mathematician and code-breaker. Back in 1952, Turing proposed a simple mathematical model in which two molecules could create patterns by spreading through tissues and interacting with each other. For example, the first molecule might activate the second, while the second blocks the first. Neither receives any guidance about where to go; through their dance, they spontaneously organize themselves into spots or stripes.

Since then, many scientists have found that these Turing mechanisms exist. They’re responsible for a cheetah’s spots and a zebrafish’s stripes. For 30 years, people have also suggested that they could sculpt our hands and feet, but no one had found the exact molecules involved.

Sharpe knew that these molecules would need to show a striped pattern. Sox9 seemed like the most promising candidate. It is activated in a striped pattern from a very early stage of development. By comparing cells where Sox9 is active or inactive, Jelena Raspopovic and Luciano Marcon found two other groups of genes—Bmp and Wnt—also formed striped patterns. Bmp rises and falls in step with Sox9 and both are active in the digits. Wnt is out of phase; it’s active in the gaps. The three molecules also affect each other: Bmp activates Sox9 while Wnt blocks it; and Sox9 blocks both of its partners. It looked like these were the molecules the team was searching for not a pair, as Turing suggested, but a trinity. To confirm this, they created a simulation of a growing limb bud and showed that Sox9, Bmp and Wnt could organize themselves into a pattern of five stripes, by activating and blocking each other.

There’s still a lot to discover, though. For example, I’ve used Bmp and Wnt as shorthands here—in reality, each represents a class of several molecules, and the team still needs to work out which specific member is part of the Turing’s proposal.