Biphasic inflammation control by fibroblasts enables spinal cord regeneration in zebrafish
Nora John,
Thomas Fleming,
Julia Kolb,
Olga Lyraki,
Sebastián Vásquez-Sepúlveda,
Asha Parmer,
Kyoohyun Kim,
Maria Tarczewska,
Kanwarpal Singh,
Frederico Marini,
Sumeet Pal Singh,
Sven Falk,
Kristian Franze,
Jochen Guck,
Daniel Wehner
Fibrosis and persistent inflammation are interconnected processes that inhibit axon regeneration in the mammalian central nervous system (CNS). In zebrafish, by contrast, fibroblast-derived extracellular matrix deposition and inflammation are tightly regulated to facilitate regeneration. However, the regulatory cross-talk between fibroblasts and the innate immune system in the regenerating CNS remains poorly understood. Here, we show that zebrafish fibroblasts possess a dual role in inducing and resolving inflammation, which are both essential for regeneration. We identify a transient, injury-specific cthrc1a+ fibroblast state with an inflammation-associated, less differentiated, and non-fibrotic profile. Induction of this fibroblast state precedes and contributes to the initiation of the inflammatory response. At the peak of neutrophil influx, cthrc1a+ fibroblasts coordinate the resolution of inflammation. Disruption of these inflammation dynamics alters the mechano-structural properties of the lesion environment and inhibits axon regeneration. This establishes the biphasic inflammation control by dedifferentiated fibroblasts as a pivotal mechanism for CNS regeneration.
Selective plane illumination microscopy (SPIM), also known as light sheet fluorescence microscopy, provides high specificity through fluorescence labeling. However, it lacks complementary structural information from the surrounding context, which is essential for the comprehensive analysis of biological samples. Here, we present a high-resolution, multimodal imaging system that integrates SPIM with full-field optical coherence tomography (FF-OCT), without requiring modifications to the existing SPIM setup. Both SPIM and FF-OCT offer low phototoxicity and intrinsic optical sectioning, making them well-suited for in vivo imaging. Their shared detection path enables seamless and efficient co-registration of fluorescence and structural data. We demonstrate the functionality of this combined system by performing in vivo imaging of zebrafish larvae.
Femtosecond Fieldoscopy for super-resolution label-free microscopy
Soyeon Jun,
Andreas Herbst,
Kilian Scheffter,
Daniel Wehner,
Anchit Srivastava,
Hanieh Fattahi
Accessing complete electric field information of a laser pulse interacting with a medium at visible to near-infrared (near-petahertz) frequencies has traditionally required complex laboratory systems operating in vacuum conditions. Recent advancements, however, have enabled the measurement of electric fields at near-petahertz frequencies in ambient air. This capability is critical for understanding ultrafast phenomena and for achieving quantitative detection of molecular species in various samples. This article introduces Femtosecond Fieldoscopy, a field-resolved detection technique for label-free spectroscopy and microscopy. This approach delivers exceptional detection sensitivity and dynamic range at petahertz bandwidths by combining attosecond temporal resolution with temporal isolation of target molecular responses from environmental and excitation pulse effects. Furthermore, Femtosecond Fieldoscopy holds promise for achieving sub-diffraction spatial resolution, opening new horizons for high-precision label-free spectro-microscopy.
Kontakt
Forschungsgruppe Daniel Wehner
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen
