Modes of Morphogen Cooperation for Limb Formation in Vertebrates and Insects

Abstract

Diffusing morphogens in cooperation can control gene expression in developing limbs. Additive cooperation corresponds to the Boolean operator OR and implies the equivalent action of the (suitably scaled) concentrations of two morphogens, either by their alternative binding to the same receptor or by another way of convergence of their effects during the signal transduction procedure. This cooperation can explain the spatial and temporal collinearities of the expression ofhoxd genes in the vertebrate limb bud. A multiplicative cooperation of morphogens (corresponding to the Boolean operator AND), produced at the DPP and WG domains in the Drosophila leg imaginal disc, may account for the expression domains observed for Dll and dac . A molecular interpretation of the multiplicative morphogen cooperation is proposed. Some experiments are suggested for further testing of the model.