From, University of Basel

Will give a seminar entitled:

Investigating tissue patterning and growth by a morphogen gradient using novel synthetic protein binder tools

Abstract

From the wings of a butterfly to the fingers of a human hand, living tissues often have complex and intricate patterns. Developmental biologists have long been fascinated by the signals – called morphogens – that guide how these patterns develop. Morphogens are substances produced by groups of cells and spread to the rest of the tissue to form a gradient. Depending on where they sit along this gradient, cells in the tissue activate different sets of genes to ultimately define the position of the different parts of the tissue. Decades worth of studies into how limbs develop in animals from mice to fruit flies have revealed common principles of morphogen gradients that regulate the development of tissue patterns and growth. However, how their gradients play in this process remain debated in developmental biology.

To tackle this fundamental question, I study how Decapentaplegic (Dpp), a BMP type ligand, controls patterning and growth of the Drosophila wing disc (wing precursor) as a model system. Despite intensive studies, how Dpp/BMP acts as a morphogen remains largely unknown in part due to lack of tools that directly manipulate Dpp morphogen gradient. In this talk, I will first talk about our recent approaches to manipulate Dpp morphogen gradient in shape and time. To this end, I established unique experimental setups including a robust genome engineering platform and novel synthetic protein binder tools based on single chain variable fragment (scFv) and Designed Ankyrin Repeat Proteins (DARPins) to visualize and directly manipulate endogenous Dpp morphogen gradient in space and time. Using these tools, I discovered that, although dpp derived from the localized source is required for wing patterning and growth (Matsuda and Affolter., eLife 2017), Dpp dispersal from this source cells is not as important as previously thought (Matsuda et al., Nat Comms 2021). These surprising results challenge the long-standing dogma that morphogen dispersal is important for the entire tissue patterning and growth, and call for a revision about how Dpp/BMP acts as a morphogen. I will then briefly introduce my future research projects, in which I aim to further investigate how tissue patterning and growth are controlled in morphogen dispersal dependent and independent manner using synthetic protein binder tools.