Evidence for Local Cellular Interactions in Digital Fate Determination during Limb Development

Sonic hedgehog (SHH) is necessary and sufficient to establish anterior‐posterior polarity in the developing limb bud mesoderm. We proposed that in autopod stages of limb development the interdigits (ID) act as signaling centers to determine specific digit identity of the immediately anterior digital ray (DR). The ID signals to the distal vascularized mesenchyme of the DR called the phalanx‐forming region (PFR). I will extend the analysis of the molecular mechanisms of this interaction. And discuss data demonstrating that the chick foot digital rays 1, 2, and 3 are interchangeable with regard to their fate but cannot form digit 4. While digital ray 4 will respond predictably to anterior ID‐signals, ID4 alone is not sufficient to establish digit 4 identity. I will propose additional signaling mechanisms to establish digit 4 identity. And present data supporting the hypothesis that the PFR and the ID posterior to it establish a unique physical relationship that supersedes other signals. These data support further a model in which SHH establishes the ID‐DR sequence of the forming autopod, with subsequent specific ID signals specifying digit Identity.