AG Prof. Dr. Gossler

Research

Our group focuses on the analysis of a conserved mechanism of cell-cell communication and the identification and analysis of new proteins that are important for the formation and function of motile cilia.

Cell-cell communications play a central role in regulating growth and differentiation in multicellular organisms. A highly conserved communication pathway between cells is the Notch signaling pathway. Notch mediates local interactions between neighboring cells in a variety of different tissues and organisms and is therefore of central importance for the regulation of developmental processes and tissue homeostasis. Using the mouse as the animal model of choice and a combination of biochemical, molecular genetic and transgenic methods, we analyze the physiological roles of Notch signaling in different tissues and organs (e.g. Cordes et al., Serth et al., Hofmann et al., Feller et al, Sörensen et al.), how ligands differ in terms of their biochemical/signaling properties (Geffers et al., Preuße et al.), how properties of ligands and their interaction with receptors are modulated by post-translational modifications (Braune et al.) and which regions of ligands contribute to effective receptor activation (Schuster-Gossler et al. 2016).

Cilia are extensions of cells with a stereotypical microtubule-based structure. They can be motile or immotile and have a variety of cell type-specific structures and physiological functions. Disruption of cilia formation or function impairs important signaling pathways and leads to human diseases, collectively referred to as ciliopathies. Disruption of motile cilia function in humans causes a subset of ciliopathies known as primary ciliary dyskinesia (PCD). We have identified the homeobox transcription factor Noto as a crucial regulator of functional motile cilia formation in the early embryo (Ben Abdelkhalek et al., Beckers et al., Alten et al.) and identified genes with unknown functions that are regulated downstream of Noto and encode good candidates for novel components important for motile cilia formation and/or function (Stauber et al. 2017). Disruption of these genes in mice leads to phenotypes that resemble parts or the entire spectrum of PCD in human patients (e.g. Weidemann et al. 2016, Beckers et al. 2018, 2020, Rachev et al. 2020). Several projects focus on the biochemical and functional characterization of a number of these components both in vitro and in vivo as well as further analysis of mouse models.

Our projects were funded by the German Research Foundation (DFG).