Overlapping Roles and Collective Requirement for the Coreceptors GAS1, CDO, and BOC in SHH Pathway Function

SummarySecreted Hedgehog (HH) ligands signal through the canonical receptor Patched (PTCH1). However, recent studies implicate three additional HH-binding, cell-surface proteins, GAS1, CDO, and BOC, as putative coreceptors for HH ligands. A central question is to what degree these coreceptors function similarly and what their collective requirement in HH signal transduction is. Here we provide evidence that GAS1, CDO, and BOC play overlapping and essential roles during HH-mediated ventral neural patterning of the mammalian neural tube. Specifically, we demonstrate two important roles for these molecules: an early role in cell fate specification of multiple neural progenitors and a later role in motor neuron progenitor maintenance. Most strikingly, genetic loss-of-function experiments indicate an obligatory requirement for GAS1, CDO, and BOC in HH pathway activity in multiple tissues.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (266 K)Download as PowerPoint slideHighlights► CDO and BOC requirement in HH signaling differs between mouse and Drosophila ► SHH acts dynamically through GAS1, CDO, and BOC to maintain motor neuron progenitors ► GAS1 and BOC play a major role in SHH-dependent organization of the mammalian limb ► GAS1, CDO, and BOC are essential HH coreceptors in multiple HH-responsive tissues