Associated Principal Investigator, Institute I of Anatomy
The general research interest in the Wodarz group is to unravel the molecular mechanisms that control cell polarity in different cell types of animals. Cell polarity is a key feature of epithelia, neurons, stem cells and oocytes, to name just a few. In all these cell types polarity is the prerequisite for their functionality. Epithelial cells for example need to be polarized in order to transport substances across the epithelial barrier, and stem cells need to be polarized prior to asymmetric cell division, which results in daughter cells with different fates.
Our Research: The research activities in the Wodarz lab focus on three main topics:
1. Molecular control of cell polarity in epithelia and stem cells. The scientists are interested in the molecules that link adherens junctions with the cytoskeleton and are required for the establishment of apical-basal cell polarity. Intriguingly, a subset of these molecules is also involved in the polarization and asymmetric division of stem cells.
2. Identification of stemness factors in somatic and germ line stem cells. By a combination of genetics, cell isolation by FACS sorting, next generation RNA sequencing (RNAseq) and functional in vivo assays they aim to identify genes that are required for maintenance of the unique properties of stem cells
3. Functional characterization of Wnt coreceptors in Drosophila. The researchers have generated mutations in the Wnt coreceptors Off-track, Off-track2 and Ror and are currently analyzing their developmental function in the control of planar cell polarity and the signaling pathways downstream of these receptors.
The model organism of their research is the fruit fly Drosophila, as it is easily accessible to genetic manipulation and is very well suited for cell biological analyses using high-resolution light microscopy.
Our successes: The Wodarz lab has succeeded in identifying both core components and tissue-specific interaction partners of the so-called PAR-aPKC complex, which is crucial for the control of cell polarity in many different cell types. The scientists have furthermore unraveled the mechanism of how Bazooka/PAR-3, a core component of the complex, associates with the plasma membrane and localizes the complex to the cytocortex. In addition, they identified mechanisms of how kinases and phosphatases regulate the function of the PAR-aPKC complex.
In a different research line, they were recently able to demonstrate a function for two homologs of the vertebrate regulator of planar cell polarity, PTK7, in morphogenesis of the male genital system.
Our goals: The long term goal of Prof. Wodarz and his research team is the understanding of the molecular mechanisms that control cell polarity and how the components of this machinery interact with the proteins that regulate morphogenesis. They furthermore aim to understand how stem cells interact with their niches and maintain their developmental potential.
Our methods and techniques: In all of their projects the scientists aim to obtain answers to their questions by combining molecular biology, biochemistry and high-resolution light and electron microscopy with genetic and phenotypic analyses at the level of the whole organism. They believe that this approach is much more informative than relying exclusively on tissue culture or in vitro systems.
Figure 1: Confocal image of the follicular epithelium of a Drosophila ovary stained for DE-cadherin (red) Discs-Large (blue), Smallish-GFP (green) and DNA (white). Smallish-GFP is overexpressed in randomly induced cell clones and causes apical constriction of epithelial cells.
Figure 2: Confocal image of the embryonic neuroectoderm of Drosophila stained for Bazooka/PAR-3 (red), Miranda (blue) and DNA (green). The two large round cells at the bottom are neural stem cells (neuroblasts) at metaphase of mitosis undergoing asymmetric cell division.
Figure 3: Projection of a stack of images taken with a Light Sheet microscope of an embryo expressing a GFP fusion protein of the Wnt receptor D-Ror under control of its endogenous promoter.