Integration of notch signalling over time and space controls cell fate decisions in vertebrate mucociliary cells

Dr. Peter Walentek (CIBSS-AI), Internal Medicine IV (University Medical Center Freiburg, Faculty of Medicine)

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Cell-cell signalling influences processes at the cellular, tissue-wide and organismal levels. In organ development, homeostasis and regeneration, cell signalling regulates stemness, cell fates, differentiation and collective cell behaviour. Thus, elucidating the modes of signalling function and integration is pivotal to understand the principles of self-organization inherent to developing biological systems. In vertebrates, mucociliary epithelia line the epidermis and several inner organs, most prominently the airways. They are comprised of specialized cell types, including basal stem cells, multiciliated cells (MCCs) and secretory cells. Collectively, they provide a first-line of defense against pathogens through mucociliary clearance. Notch signalling controls cell fate specification and maintenance, i.e. it prevents MCC formation and favours secretory cell fates. Nevertheless, the complex and reiterative use of Notch signalling has kept us from gaining a complete understanding of its roles in mucociliary development, disease and regeneration.

We are investigating how appropriate signalling levels are (re-)generated during development and disease of mucociliary epithelia through cell type-specific transcriptomics, manipulation of ligands and receptor levels, and by comparative analysis of diverse vertebrate model systems (Xenopus, mice and human airway stem cells). Together, this work will provide an unprecedented integrative model of mucociliary cell type regulation and novel insights into how signalling algorithms regulate self-organization in living systems.


Publications resulting from the project:

Notch signaling induces either apoptosis or cell fate change in multiciliated cells during mucociliary tissue remodeling.
Tasca A, Helmstädter M, Brislinger MM, Haas M, Mitchell B, Walentek P.
Dev Cell. 2021; doi: 10.1016/j.devcel.2020.12.005.

ΔN-Tp63 Mediates Wnt/β-Catenin-Induced Inhibition of Differentiation in Basal Stem Cells of Mucociliary Epithelia.
Haas M, Gómez Vázquez JL, Sun DI, Tran HT, Brislinger M, Tasca A, Shomroni O, Vleminckx K, Walentek P.
Cell Rep. 2019; doi: 10.1016/j.celrep.2019.08.063.