Principles of cell and tissue organization


Understanding Endocytosis in vivo

The role of endocytic trafficking in the regulation of vertebrate development

In this project, we want to understand how endocytic trafficking regulates the development of a multicellular organism. Can the mechanistic insights on the endocytic core components gained from cell culture experiments be applied to understand complex developmental events? We use Zebrafish as a model system to investigate the role of endocytosis in regulating developmental signaling and cell adhesion. We apply a combination of standard developmental and cell biological techniques with advanced imaging and quantification methods to analyze the in vivo localization and spatiotemporal regulation of endocytic core components as well as new modulators of trafficking. With this strategy we gained further insights into the mediation of signaling specificity in Zebrafish by the endosomal adaptor protein APPL1 (Schenck et al., Cell 2008). Additional gain- and loss-of-function studies showed that interfering with endocytosis in vivo can lead to functional consequences for zebrafish development. Currently, we work on a novel Rab5 effector complex and its function in modulating signaling and cell adhesion during early Zebrafish development.

Fig. 1. BMP Activity Gradient in an early Zebrafish Gastrula.

The image shows a gastrulating Zebrafish embryo at the onset of shield formation (the early dorsal organizer in fish). This embryo was fixed and immuno-stained with a P-Smad1/5/8 specific antibody. The nuclear signal of that antibody is a reporter for the BMP signaling pathway. The signal is highest on the ventral side of the embryo (upper left corner) and drops drastically towards the dorsal part (lower right corner). With this assay we can record the signaling activity in shield stage embryos on a systems level across the whole embryo.

Zerial lab