Shh is out on a limb

Cells in the developing limb escape a positive feedback loop by growing a nonresponsive barrier of cells. This timing mechanism that limits both limb size and digit number is described by Paul Scherz, Clifford Tabin (Harvard Medical School, Boston, MA), and colleagues.

The number of fingers that grow on a hand is set by the Shh morphogen. Shh is made by cells in a zone at the posterior of the limb bud and sets the anterior–posterior axis by telling neighboring cells to make another morphogen, called Gremlin. Gremlin instructs the tip of the bud to express Fgf, which promotes limb outgrowth and Shh expression.

Escape from this loop in chicks depends on a newly discovered property of Shh-producing cells. Neither they nor their descendents make...