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Walther, R.

Publications and source records attributed to Walther, R..

2 recordsLinked to original sources

Transmembrane signalling by a bionic receptor: biological input and output, chemical mechanism of signal transduction

Signal transduction through sealed biological membranes is among the most important evolutionary achievements. Herein, we focus on the development of artificial signal transduction mechanisms and engineer a bionic receptor with capacity of transduction of biological signals across biological membranes using tools of chemistry. The bionic receptor described in this work exhibits similarity with the natural counterpart in the most essential characteristics: in having an exofacial ligand for signal capture, in being membrane anchored, and in featuring a releasable secondary messenger molecule, which performs enzyme activation in the endo volume. The main difference with the natural receptors is that signal transduction across the lipid bilayer was performed using the tools of organic chemistry, namely a self-immolative linker. The highest novelty of our work is that the artificial signalling cascade designed herein achieved transmembrane activation of enzymatic activity, as is the hallmark of activity by natural signalling receptors.

synthetic biology↗

Neph/Nephrin-like adhesion and tissue level pulling forces regulate cell intercalation during Drosophila retina development.

Intercalation between neighboring cells contributes to shaping epithelial tissues and is regulated by the contractile actomyosin cytoskeleton. While intercalation typically occurs over minutes, instances of much slower cell intercalation have been reported during organogenesis. This is observed, for example, for the four glial-like cone cells (CC) that intercalate during Drosophila retinal patterning. Here we show that Myosin-II activity in the CCs is largely dispensable for their intercalation. Instead, we find that differential activity of the Notch-signaling pathway within the CC quartet regulates intercalation, which also depends on the cell adhesion proteins Roughest and Hibris. In addition, mathematical modeling predicts that forces external to the intercalating CC quartet are necessary for intercalation. Consistent with this prediction we show that the surrounding primary pigment cells are under significant contractile tension. Altogether, our work elucidates a novel mode of cell intercalation that relies on Neph/Nephrin-like adhesion and forces external to the intercalating cells.

developmental biology↗