Self-Induced Patched Receptor Down-Regulation Modulates Cell Sensitivity to the Hedgehog Morphogen Gradient

Abstract

Morphogens form signaling gradients that control patterning processes during development. Responding cells must perceive and interpret the concentration-dependent information provided by the morphogen to generate precise patterns of gene expression and cell differentiation in developing tissues. Generally, the absolute number of activated, ligand-bound receptors determines cell perception of the morphogen. In contrast, cells interpret the morphogen Hedgehog (Hh) by measuring the ratio of bound to unbound molecules of its receptor Patched (Ptc). This ratio depends on both the Hh concentration and the absolute number of Ptc molecules. Here, I describe a posttranscriptional process that controls the absolute amount of Ptc present in a cell, which regulates gradient interpretation, wherein self-induced receptor down-regulation that is independent of ligand binding dictates the cell response to a morphogen gradient.