Defining digit number in the limb Free

During vertebrate limb development, multiple mechanisms act to ensure the appropriate number, identity and positioning of digits. In both the chick and the mouse, Sonic hedgehog (Shh) signalling emanating from the posterior polarising region provides positional information and regulates tissue expansion, while a self-organising Turing-type mechanism has been proposed to account for digit number determination. However, we still have an incomplete understanding of how these mechanisms interact, and how they have been manipulated during evolution to generate different species with different numbers and types of digit. On p. 3514, Joseph Pickering and Matthew Towers use temporally defined application of the Shh inhibitor cyclopamine to the chick wing to explore these questions. They find that, surprisingly, Shh inhibition at a specific time point can lead to an increased digit number, as well as increased proliferation of the polarising region. Moreover, they observe posterior expansion of the overlying apical ectodermal ridge (AER) – the source of Fgf signalling that is also key for digit formation. The data suggest that, if Shh signalling is inhibited during this critical period, there is a switch from Shh-dependent anterior-posterior expansion to AER-dependent expansion, with consequent effects on digit number and patterning. Together, these data help to shed light on the evolutionary mechanisms resulting in the divergence in digit patterning across vertebrates.