Research in my laboratory focuses on mechanisms of cell polarization. Cellular polarity is an important feature of cellular organization in uni- and multicellular organisms. Defective cell polarization leads to organ malformations and many diseases including cancer. At first
glance, the repertoire of cell polarity seems rather diverse. Migrating cells exhibit a trailingand leading-edge polarity; epithelial cells are characterized by a apico-basal polarity, and neurons by a axonal-somatodendritic polarity etc. Although a number of molecular polarity factor have been identified that are common to all these different polarization type, very little is known on the sensing and interpreting of outside cues by these intracellular factors and the subsequent formation of polarized cells in seemingly very diverse cellular environments.
We focus on the so-called planar cell polarity (or in short: PCP) pathway that polarizes cells
in the plane of a tissue. In epithelia, the PCP pathway acts perpendicular to the apico-basal
pathway and also shows molecular interactions with apico-basal determinants. Genetic
screens in Drosophila melanogaster have identified a set of conserved PCP core factors.
Mutations in these factors lead to defects in wing hair patterning, sensory bristle orientation
in the notum and abdomen, and ommatidial rotation in the eye. More recently, many
vertebrate tissues and developmental processes have also been shown to display typical
PCP features and to be regulated by the same core factors as those in Drosophila.
Generally, tissues that develop cellular appendages such as inner ear sensory cells use PCP to organize their alignment. Furthermore, collective directional cell migration and tissue fusion processes, as found in gastrulation or in epidermal wound healing, respectively, are important PCP-dependent event. As a consequence, defective PCP signalling contributes to many diseases including neural tube defects or polycystic kidney disease.
Recent data from our laboratory suggests that proton transport is crucial for PCP protein
trafficking and localization. Our research has focussed on an accessory subunit of the VATPase, ATP6AP2 (or VhaPRR), functions in planar cell polarity (PCP) signalling in
Drosophila. This project has led us to study the role of the V-ATPase in other cellular
processes, such as cell migration and invasion. As experimental systems, we are using
various Drosophila tissues as well human breast cancer cell lines and keratinocytes. We are working at the interface of biophysics, cell, developmental and systems biology combining genetics with live imaging and mathematical modeling. An important experimental aim is to measure local pH in specific organelles or in specific parts of the cytosol. This technique is performed in cultured cells and diverse fly tissues.
1. Hermle T, Guida MC, Beck S and Simons M: Drosophila ATP6AP2/VhaPRR functions
both in planar cell polarity and endosomal trafficking, minor revision
2. Hermle T, Saltukoglu D, Grünewald J, Walz G, Simons M: Regulation of Frizzled-
Dependent Planar Polarity Signaling by a V-ATPase Subunit, Current Biology 2010
Jul 27(20); 1269-74.
3. Simons M, Gault W, Klein TJ, Gotthardt D, Shao Y, Wu AL, Fang Y, Dow J, Chen J,
Zheng J, Boutros M, Mlodzik M: Electrochemical cues regulate the assembly of the
Fz/Dsh complex at the plasma membrane during planar epithelial polarization, Nature
Cell Biology 2009 Mar 11(3):286-94.
4. Simons M*, Gloy J*, Ganner A, Bullerkotte A, Bashkurov M, Schermer B, Benzing T ,
Cabello OA, Polok B, Driever W, Jenny A, Mlodzik M, Obara T, Walz G: Inversin, the
nephronophthisis type II gene product, functions as a switch molecule between Wnt
signaling pathways, Nature Genetics 2005 May;37(5):537-43.
planar cell polarity – pH regulation – directional migration – V-ATPase – cell protrusions
Always looking for motivated PhD students and Postdocs