DECODING MORPHOGEN-INSTRUCTED DEVELOPMENTAL PRECISION

Abstract

This thesis tackles the question of how developmental precision is intrinsically encoded within the way cells interpret morphogen gradients. The first major theme is to dissect the temporal integration of morphogen-encoded information by cells in developing embryos. Using the morphogen Bicoid in early Drosophila embryo as a model system, an optogenetic technique to temporally manipulate Bicoid transcriptional activity is developed. It is observed that cells instructed by higher morphogen concentration also require morphogen inputs for longer duration, and such temporal non-linearity of morphogen interpretation can be at least partially attributed to differential kinetics of target gene activation. The second theme concerns the loss of developmental precision under decanalized conditions, for example, where morphogen inputs are perturbed. It is argued here that the mechanical properties, such as the embryonic geometry introduces sources of variation into the patterning process, and therefore predetermines the phenotypic outcomes of each perturbed individual.