Biology subjects

Knaus, P.

Publications and source records attributed to Knaus, P..

3 recordsLinked to original sources

bioRxiv2023

Reorganization of Septin structures regulates early myogenesis

Controlled myogenic differentiation is crucial for developmental formation, homeostatic maintenance and adult repair of skeletal muscle and relies on cell fate determinants in myogenic progenitors or resident stem cells. Proliferating muscle progenitors migrate, adopt spindle shape, align membranes and fuse into multinuclear syncytia. These processes are accompanied by cyto-architectural changes driven by rearranging of cytoskeletal components such as actin and microtubules. Here we highlight septins, the fourth component of the cytoskeleton, to represent an essential structural element of myoblasts. Specifically, Septin9 regulates myoblast differentiation during the early commitment process. Depletion of Septin9 in C2C12 cells and primary myoblasts led to a precocious switch from a proliferative towards a committed progenitor transcriptomic program. Additionally, we report Septin9 undergoing substantial reorganization and downregulation during myogenic differentiation. Together, we propose filamentous septin structures and their controlled reorganization in myoblasts to provide a key temporal regulation mechanism for the differentiation of myogenic progenitors.

cell biology↗

bioRxiv2022

Odd skipped-related 1 controls the pro-regenerative response of Fibro-Adipogenic Progenitors

Skeletal muscle regeneration requires the coordinated interplay of diverse tissue-resident- and infiltrating cells. Fibro-adipogenic progenitors (FAPs) are an interstitial cell population that provides a beneficial microenvironment for muscle stem cells (MuSCs) during muscle regeneration. Here we show that the transcription factor Osr1 is essential for FAPs to communicate with MuSCs and infiltrating macrophages, thus coordinating muscle regeneration. Conditional inactivation of Osr1 impaired muscle regeneration with reduced myofiber growth and formation of excessive fibrotic tissue with reduced stiffness. Osr1-deficient FAPs acquired a fibrogenic identity with altered matrix secretion and cytokine expression resulting in impaired MuSC viability, expansion and differentiation. Immune cell profiling suggested a novel role for Osr1-FAPs in macrophage polarization. In vitro analysis suggested that increased TGF{beta} signaling and altered matrix deposition by Osr1-deficient FAPs actively suppressed regenerative myogenesis. In conclusion, we show that Osr1 is central to FAP function orchestrating key regenerative events such as inflammation, matrix secretion and myogenesis.

developmental biology↗

bioRxiv2022

A versatile Halo- and SNAP-tagged BMP/TGFβ receptor library for quantification of cell surface ligand binding

The TGF{beta} superfamily of secreted growth factors comprises more than 30 members including TGF{beta}s, BMPs and Activins. While all TGF{beta} superfamily members signal through heteromeric receptor complexes to regulate a plethora of developmental and homeostatic processes, each ligand possesses a unique affinity towards a subset of BMP and TGF{beta} type I and type II receptors. Whereas the Activin and TGF{beta} class display a higher affinity towards type II receptors, BMPs and GDFs preferentially bind to type I receptors. Sofar, the lack of specific antibodies and chemical biology tools hampered simultaneous testing of ligand binding towards all BMP and TGF{beta} receptors. Here we present a N-terminally Halo- and SNAP-tagged TGF{beta}/BMP receptor library to visualize the receptor complexes in dual color. In combination with novel fluorescently labeled TGF{beta} superfamily ligands, we established a Ligand Surface Binding Assay (LSBA) for optical quantification of receptor-dependent growth factor binding for Activin A, TGF{beta}1 and BMP9 in a cellular context. We confirm ligand-receptor interface specificity by identifying BMPR2- or ALK2-mutants that switch from a low-affinity Activin A- or BMP9-receptor to a high-affinity receptor, respectively.

cell biology↗