Molecular Embryology

  • Cell and Tumor Biology
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Prof. Dr. Christof Niehrs

Division Head

How cells communicate with their environment via cell-cell interactions and by growth factors is a key question in the molecular life sciences, including tumor biology. Wnt signaling plays an important role in embryonic development and cancer. In the Division of Molecular Embryology we study mechanisms of Wnt pathway regulation. To this end, we identify developmental control genes, investigate what their biological role and biochemical mode of action is, and how the genes are regulated.

An abstract, colorful representation of molecular structures, featuring intricate yellow and blue filament-like entities extending from a darker surface. This image illustrates the complex interactions at a microscopic level, emphasizing the beauty of biological systems. A scale bar indicates a size of 50 nanometers.

Lines of Research:

Diagram illustrating Ciliary Wnt signaling. It features components such as Wnt, CCNY/IL1, LRP6, and signaling pathways leading to the formation of primary cilia, multicilia, and flagella. Important proteins GSK3, PPP1R*, and PP1 are also included.
A conserved ciliary Wnt-PP1 signaling axis. Primary- cilia, multicilia, and flagella share a distinct ciliary Wnt signaling axis. The PP1 regulatory subunit may differ between primary- (PPP1R2) and motile multicilia (PPP1R11). © dkfz.de

In processes ranging from larval development to respiration, mucociliary membranes defend epithelia against irritants and pathogens by a directional mucous flow generated through the coordinated beating of motile cilia. Deficiency of these nanopropellers leads to airway disease and ciliopathies, and understanding their cell biology is important for the rational design of cilio-stimulatory therapies. Hence, understanding their cell biology is important for the rational design of cilio-stimulatory therapies.

Cilia and Wnt signaling have a complex relationship, wherein Wnt regulates cilia and, conversely, cilia may affect Wnt signaling. Recently, we showed that Wnt receptors are present in flagella, primary cilia, and multicilia, where they transmit an intraciliary signal that is independent of β-catenin. Intraciliary Wnt signaling promotes ciliogenesis, affecting male fertility, adipogenesis, and mucociliary clearance. Wnt also stimulates the beating of motile cilia, highlighting that these nanomotors too, are chemosensory. Intraciliary Wnt signaling employs a Wnt- protein phosphatase 1 (PP1) signaling axis, involving the canonical Wnt pathway's inhibition of GSK3 to repress PP1 activity. Collectively, these findings support that cilia are Wnt signaling organelles, with implications for ciliopathies and cancer.

Our working hypothesis is that Wnt ┫PP1 signaling is physiologically relevant in other mammalian ciliated cells and tissues. To answer in which physiological processes and tissues does primary and mucociliary Wnt signaling play a role in e.g. mouse, we need to deconvolute the requirement for Wnt signaling in the plethora of other tissues and processes wherein the pathway is involved from those where specifically ciliary Wnt signaling is involved. Towards this end we are studying mouse mutants in which components specific for ciliary Wnt signaling are inactivated.

References

 

  1. Zhang K, Da Silva F, Seidl C, Wilsch-Bräuninger M, Herbst J, Huttner WB, Niehrs C. (2023) Primary cilia are WNT-transducing organelles whose biogenesis is controlled by a WNT-PP1 axis. Dev Cell 58:139-154.
  2. Seidl C, Da Silva F, Zhang K, Wohlgemuth K, Omran H, Niehrs C. (2023) Mucociliary Wnt signaling promotes cilia biogenesis and beating. Nat Commun. 6; 14:1259.
  3. Niehrs C, Da Silva F, Seidl C. (2024) Cilia as Wnt signaling organelles. Trends Cell Biol. doi: 10.1016/j.tcb.2024.04.001

Team

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    Prof. Dr. Christof Niehrs

    Division Head

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    Ahmed Ibrahim Akhtar

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    Dr. Katja Baur

    Postdoctoral Scientist

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    Katharina Block

    Trainee

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    Celine Camuto

    Doctoral Researcher

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    Deniz Citakci

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    Dr. Tianshu Gui

    Postdoctoral Scientist

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    Jessica Herbst

    Technician

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    Dr. Nedasadat Kazemeinjasemi

    Postdoctoral Scientist

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    Piotr Kluska

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    Dr. Hyeyoon Lee

    Postdoctoral Scientist

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    Dr. Romina Ines Minen

    Postdoctoral Scientist

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    Carmen Reinhard

    Technician

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    Angelika Schmidt-Zitouni

    Secretary

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    Dr. Lars Schomacher

    Postdoctoral Scientist

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    Myrthe Visser

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    Tianheng Zhu

    Doctoral Researcher

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Prof. Dr. Christof Niehrs

Division Head
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