Quantitative insight into models of Hedgehog signal transduction.

The Hedgehog (Hh) signaling pathway is an essential regulator of embryonic development and a key factor in carcinogenesis.(1,2) Hh, a secreted morphogen, activates intracellular signaling events via downstream effector proteins, which translate the signal to regulate target gene transcription.(3,4) In a recent publication, we quantitatively compared two commonly accepted models of Hh signal transduction.(5) Each model requires a different ratio of signaling components to be feasible. Thus, we hypothesized that knowing the steady-state ratio of core signaling components might allow us to distinguish between models. We reported vast differences in the molar concentrations of endogenous effectors of Hh signaling, with Smo present in limiting concentrations.(5) This extra view summarizes the implications of this endogenous ratio in relation to current models of Hh signaling and places our results in the context of recent work describing the involvement of guanine nucleotide binding protein Galphai and Cos2 motility.