- Neuroscience of respiration and sleep
- Zebrafish Biomedical Research Applications
- Neurobiology and Insect Physiology Research
- Nerve injury and regeneration
- Neonatal Respiratory Health Research
- Signaling Pathways in Disease
- Axon Guidance and Neuronal Signaling
- Cellular Mechanics and Interactions
- Primate Behavior and Ecology
- Neuropeptides and Animal Physiology
- Infant Health and Development
- Developmental Biology and Gene Regulation
- Neural dynamics and brain function
- Neurogenesis and neuroplasticity mechanisms
- Physiological and biochemical adaptations
- Children's Physical and Motor Development
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Wnt/β-catenin signaling in development and cancer
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Hippo pathway signaling and YAP/TAZ
- Gastroesophageal reflux and treatments
- RNA Research and Splicing
Max Delbrück Center
2017-2024
Charité - Universitätsmedizin Berlin
2018-2022
Howard Hughes Medical Institute
2011-2014
Columbia University
2010-2011
New York University
2003-2009
Institute of Neurobiology and Molecular Medicine
2005
Fibroblast growth factors (FGFs) interact with heparan sulfate glycosaminoglycans and the extracellular domains of FGF cell surface receptors (FGFRs) to trigger receptor activation biological responses. homologous (FHF1-FHF4; also known as FGF11-FGF14) are related FGFs by substantial sequence homology, yet their only documented interactions an intracellular kinase scaffold protein, islet brain-2 (IB2) voltage-gated sodium channels. In this report, we show that recombinant FHFs can bind...
Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions many distinct subtypes of vagal neurons. Here, we use genetically guided anatomical tracing, optogenetics, electrophysiology identify characterize neuron expressing Prox2 Runx3 mice. We show that three these neuronal innervate esophagus stomach regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological...
The p75 neurotrophin receptor (p75(NTR)), a member of the tumor necrosis factor superfamily receptors, undergoes multiple proteolytic cleavage events. These events are initiated by an alpha-secretase-mediated release extracellular domain followed gamma-secretase-mediated intramembrane cleavage. However, specific determinants p75(NTR) unknown. Many other substrates gamma-secretase have been identified, including Notch, amyloid precursor protein, and ErbB4, indicating there is broad substrate...
Neurotrophins are trophic factors that regulate important neuronal functions. They bind two unrelated receptors, the Trk family of receptor-tyrosine kinases and p75 neurotrophin receptor (p75). was recently identified as a new substrate for gamma-secretase-mediated intramembrane proteolysis, generating p75-derived intracellular domain (p75-ICD) with signaling capabilities. Using PC12 cells model, we studied how neurotrophins activate processing where these events occur in cell. We...
Significance Vocalization is a primary method of communication in many species and relies on coordinated muscle activity. breathing must be synchronized, because calls can evoked only during expiration. How vocalization are not well understood. Here, we show that newborn mice with impaired development the nucleus tractus solitarius (NTS) mute cannot generate expiratory pressure needed for vocalization. Furthermore, they do receive appropriate maternal care. We demonstrate NTS contains...
Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons regulated a network of interneurons within the spinal cord, but computational processes involved in control not fully understood. The neuroanatomical arrangement and premotor into topographic patterns related to their muscles is thought facilitate how information processed circuits. Rabies retrograde monosynaptic tracing has been used label innervating specific pools, with...
Propriospinal neurons relay sensory and motor information across the spinal cord are critical components of circuits coordinating body movements. Their diversity roles in control not clearly defined yet. In this study, by combining anatomical, molecular, functional analyses mice, we identified characterized an ascending subtype propriospinal belonging to Pitx2+ V0 family neurons. We found that integrated sensorimotor their function is important for execution precise limb movements required...
Regulation of cell survival decisions and neuronal plasticity by neurotrophins are mediated two classes receptors, Trks (tropomyosin receptor kinases) p75, the first discovered member tumour necrosis factor superfamily. The p75 participates with TrkA in formation high-affinity nerve growth factor-binding sites to promote under limiting concentrations neurotrophins. Activation Trk receptors leads increased phosphorylation Shc (Src homology collagen homology), phospholipase C-gamma novel...
Abstract The precise execution of coordinated movements depends on proprioception, the sense body position in space. However, molecular underpinnings proprioceptive neuron subtype identities are not fully understood. Here we used a single-cell transcriptomic approach to define mouse proprioceptor subtypes according identity muscle they innervate. We identified and validated signatures associated with proprioceptors innervating back ( Tox , Epha3 ), abdominal C1ql2 hindlimb Gabrg1 Efna5 )...
Motor neurons in the spinal cord are found grouped nuclear structures termed pools, whose position is precisely orchestrated during development. Despite emerging role of pool organization assembly circuits, little known about morphogenetic programs underlying patterning motor neuron subtypes. We applied three-dimensional analysis to reveal roles and contributions cell adhesive function by inactivating N-cadherin, catenin, afadin signaling. Our findings that dependent on inside-out...
Breathing, and the motor circuits that control it, is essential for life. At core of respiratory are Dbx1-derived interneurons, which generate rhythm pattern breathing, phrenic neurons (MNs), provide final output drives diaphragm muscle contractions during inspiration. Despite their critical function, principles dictate how assemble unknown. Here, we show coordinated activity a type I cadherin (N-cadherin) II cadherins (Cadherin-6, -9, -10) required in both MNs to robust output. Both MN-...
Afadin, a scaffold protein controlling the activity of nectin family cell adhesion molecules, regulates important morphogenetic processes during development. In central nervous system, afadin has critical roles in neuronal migration, axonal elongation, and synapse formation. Here we examine role development spinal motor circuits. Afadin elimination neuron progenitors results striking locomotor behavior: left-right limb alternation is substituted by synchronous activation, characteristic...
Type I and type II classical cadherins constitute a family of cell adhesion molecules expressed in complex combinatorial profiles the nervous system, suggesting hypothesis that cadherin code implements specific adhesive recognition events control development neural circuits. In spinal cord, define at molecular level positional organization motor neuron subtypes into discrete nuclear structures termed pools. However, roles contributions different members defining spatial are not clear yet. By...
The precise pattern of motor neuron (MN) activation is essential for the execution actions; however, molecular mechanisms that give rise to specific patterns MN activity are largely unknown. Phrenic MNs integrate multiple inputs mediate inspiratory during breathing and constrained fire in a drives efficient diaphragm contraction. We show Hox5 transcription factors shape phrenic output by connecting inhibitory premotor neurons. genes establish organization dendritic topography through...