A5065262725- Axon Guidance and Neuronal Signaling
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Traumatic Brain Injury and Neurovascular Disturbances
- Advanced Fluorescence Microscopy Techniques
- S100 Proteins and Annexins
- Zebrafish Biomedical Research Applications
- Cellular Mechanics and Interactions
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Supramolecular Self-Assembly in Materials
- Multiple Sclerosis Research Studies
- Bone Metabolism and Diseases
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- Olfactory and Sensory Function Studies
- Advanced biosensing and bioanalysis techniques
- Neuroblastoma Research and Treatments
- Traumatic Brain Injury Research
- Sirtuins and Resveratrol in Medicine
- Facial Nerve Paralysis Treatment and Research
- Neurological Disorders and Treatments
Universität Ulm
2015-2024
Institute of Neurobiology
2023
University of Tübingen
2005-2014
TH Bingen University of Applied Sciences
2009
Medical Research Council
2003-2006
King's College London
2002-2005
Guy's Hospital
2003
Max Planck Institute for Developmental Biology
2001
Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes, including cell cycle progression and cytoskeletal dynamics. A limited number of Cdk substrates have been identified with few demonstrated to be regulated by Cdk-dependent phosphorylation. We identify on protein expression arrays novel cyclin E–Cdk2 substrates, SIRT2, a member the Sirtuin family NAD+-dependent deacetylases that targets α-tubulin. define Ser-331 as site phosphorylated E–Cdk2, A–Cdk2, p35–Cdk5...
Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a ( Sprr1a ) , Galanin Gal growth-associated 43 Gap43 )) facilitating axon regeneration. We provide first analysis of mouse mutants nerve In mutant mice, facial regeneration neurite outgrowth adult ATF3-deficient primary dorsal root...
Significance How transcription factors (TFs) activate is a long-standing but still unsolved question. We analyzed serum response factor (SRF), stimulus-responsive TF mediating immediate early gene (IEG) and cytoskeletal expression at single-molecule resolution. Cell stimulation enhanced SRF activity by increasing the number of long chromatin-associated molecules in an oscillating pattern. Further, chromatin residence time, binding events segregated into three distinct time regimes (short,...
Abstract Immune system molecules are expressed by neurons, yet their functions often unknown. We have identified IL-13 and its receptor IL-13Ra1 as neuronal, synaptic proteins in mouse, rat, human brains, whose engagement upregulates the phosphorylation of NMDAR AMPAR subunits and, turn, increases activity CREB-mediated transcription. demonstrate that increased is a hallmark traumatic brain injury (TBI) male mice well two distinct cohorts patients. also provide evidence upregulation protects...
ABSTRACT We have investigated the role of Eph family receptor tyrosine kinases and their ligands in establishment vomeronasal projection mouse. Our data show intriguing differential expression patterns ephrin-A5 on axons EphA6 accessory olfactory bulb (AOB), such that with high ligand concentration project onto regions AOB vice versa. These suggest a mechanism for development this is opposite repellent interaction between receptors observed other systems. In support idea, when given choice...
EphA receptor tyrosine kinases and their ephrin ligands play important roles in wiring of the developing nervous system. We have investigated here function Src family (SFKs) retinotectal projection to dissect signaling pathways by which receptors control actin/microtubule rearrangements that underlie growth cone guidance collapse. Both EphAs SFKs are expressed broadly retinal cones, recruited after ephrinA stimulation. In stripe collapse assays we observe an abolition EphA-mediated repulsion...
Genetic variations in TMEM106B, coding for a lysosomal membrane protein, affect frontotemporal lobar degeneration (FTLD) GRN- (coding progranulin) and C9orf72-expansion carriers might play role aging. To determine the physiological function of we generated TMEM106B-deficient mice. These mice develop proximal axonal swellings caused by drastically enlarged LAMP1-positive vacuoles, increased retrograde transport lysosomes, accumulation lipofuscin autophagosomes. Giant vacuoles specifically...
Abstract The synthesis of hybrid hydrogels by pH‐controlled structural transition with exceptional rheological properties as cellular matrix is reported. “Depsi” peptide sequences are grafted onto a polypeptide backbone that undergo pH‐induced intramolecular O–N–acyl migration at physiological conditions affording nanofibers (PNFs) supramolecular gelators. polypeptide–PNF mechanically remarkably robust. They reveal exciting thixotropic behavior immediate in situ recovery after exposure to...
A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos Egr1.We employed the mouse pilocarpine model to analyze transcription factor (TF) serum response (SRF) epileptogenesis, seizure induced histopathology IEG induction. SRF a regulated TF stimulating well nerve growth guidance. Adult conditional deficient mice...
Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in astrocyte and microglia activation at the lesion site. This involves upregulation of genes, including chemokines interleukins. However, so far, there is lack knowledge on transcription factors (TFs) modulating this TBI-associated gene expression response. Herein, we analyzed activating factor 3 (ATF3), TF encoding regeneration-associated (RAG) predominantly studied peripheral nervous system (PNS) injury. ATF3...
Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain such as neurons. Herein, we analyzed FTY720's potential directly alter neuronal function. In CNS neurons, identified governed gene expression response. upregulated immediate early genes (IEGs) encoding activity associated transcription factors c-Fos, FosB, Egr1 and Egr2 induced actin cytoskeleton (actin isoforms,...
Neuronal motility relies on actin treadmilling. In addition to regulating cytoskeletal dynamics in the cytoplasm, modulates nuclear gene expression. We present a hitherto unappreciated cross talk of signaling with expression governing neuronal motility. Toward this end, we used novel approach using mutant actins either favoring (G15S) or inhibiting (R62D) F-actin assembly. Overexpressing these mouse hippocampal neurons not only modulated growth-cone function but also neurite elongation,...
Aberrant mitochondrial function, morphology, and transport are main features of neurodegenerative diseases. To date, within neurons is thought to rely mainly on microtubules, whereas actin might mediate short-range movements anchoring. Here, we analyzed the impact neuronal size localization. F-actin enhanced number in neurites growth cones. In contrast, raising G-actin resulted fragmentation decreased abundance. Cellular F-actin/G-actin levels also regulate serum response factor...
During brain development, neurons and their nerve fibers are often segregated in specific layers. The hippocampus is a well-suited model system to study lamination health aberrant cell/fiber associated with neurological disorders. SRF (serum response factor), transcription factor, regulates synaptic-activity-induced immediate-early gene (IEG) induction cytoskeleton-based neuronal motility. Using early postnatal conditional ablation, we uncovered distorted hippocampal lamination, including...