'Big frog, small frog'- maintaining proportions in embryonic development: Delivered on 2 July 2008 at the 33^rd FEBS Congress in Athens, Greece

We discuss mechanisms that enable the scaling of pattern with size during the development of multicellular organisms. Recently, we analyzed scaling in the context of the early Xenopus embryo, focusing on the determination of the dorsal-ventral axis by a gradient of BMP activation. The ability of this system to withstand extreme perturbation was exemplified in classical experiments performed by Hans Spemann in the early 20th century. Quantitative analysis revealed that patterning is governed by a noncanonical 'shuttling-based' mechanism, and defined the feedback enabling the scaling of pattern with size. Robust scaling is due to molecular implementation of an integral-feedback controller, which adjusts the width of the BMP morphogen gradient with the size of the system. We present an 'expansion-repression' feedback topology which generalizes this concept for a wider range of patterning systems, providing a general, and potentially widely applicable model for the robust scaling of morphogen gradients with size.