It takes time to make a pinky: unexpected insights into how SHH patterns vertebrate digits

It is widely accepted that the diffusible Sonic Hedgehog (SHH) morphogen signal establishes a spatial gradient that patterns embryonic structures by long-range signaling. In response, cell fates are determined by linear thresholds according to the position of cells within the gradient field. Two recent studies of SHH signaling during vertebrate limb development challenge this spatial gradient model. They establish that a large fraction of limb bud cells patterned by SHH are descendants of cells that have previously expressed Shh. These cells are endowed with a kinetic memory that integrates their exposure to SHH rather than sensing their position in a SHH gradient. In addition, a fraction of cells changes their SHH responsiveness progressively during limb bud pattering, which is indicative of local nonlinear modulation of cell fate specification.