A5042285286- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Stress Responses and Cortisol
- Neuroendocrine regulation and behavior
- Adipose Tissue and Metabolism
- Neuropeptides and Animal Physiology
- Single-cell and spatial transcriptomics
- Animal Genetics and Reproduction
- Axon Guidance and Neuronal Signaling
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Neural dynamics and brain function
- Hormonal Regulation and Hypertension
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- Alzheimer's disease research and treatments
- HER2/EGFR in Cancer Research
- Memory and Neural Mechanisms
- Signaling Pathways in Disease
- Cell Image Analysis Techniques
- Tryptophan and brain disorders
- Retinoids in leukemia and cellular processes
- Neuroscience of respiration and sleep
- Pain Mechanisms and Treatments
- Antimicrobial Peptides and Activities
Salk Institute for Biological Studies
2014-2025
University of California, San Diego
2004-2021
Torrey Pines Institute For Molecular Studies
1997-2007
University of Virginia Health System
2007
Acceleron Pharma (United States)
2007
Neurocrine Biosciences (United States)
2007
Yale University
2002-2004
Baldwin Wallace University
2004
Oregon Health & Science University
2004
University of California, San Francisco
2004
Phosphorylation of inhibitor kappa B (IkappaB) proteins is an important step in the activation transcription nuclear factor (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) IKK2 (IKKbeta). Mice that are devoid gene had extensive liver damage from apoptosis died as embryos, but these mice could be rescued by inactivation encoding tumor necrosis receptor 1. Mouse embryonic fibroblast cells were isolated IKK2-/- embryos showed a marked reduction factor-alpha (TNF-alpha)-...
Corticotropin-releasing factor (CRF) and its family of peptides are critical coordinators homeostasis whose actions mediated through their receptors, CRF receptor 1 (CRFR1) CRFR2, found throughout the CNS periphery. The phenotypes mice deficient in either CRFR1 or CRFR2 demonstrate role these receptors play. CRFR1-mutant have an impaired stress response display decreased anxiety-like behavior, whereas CRFR2-mutant hypersensitive to increased behavior. To further elucidate roles both...
ABSTRACT To understand the role of low-affinity neurotrophin receptor p75 in neural development, we previously generated mice carrying a null mutation locus (Lee, K. F., Li, E., Huber, L. J., Landis, S. C., Sharpe, A. H., Chao, M. V. and Jaenisch, R. (1992) Cell 69, 737 –749). elucidate mechanisms leading to deficits peripheral nervous system mutant mice, have employed dissociated cultures examine responses p75-deficient dorsal root ganglion (DRG) superior cervical (SCG) neurons different...
The low-affinity neurotrophin receptor p75 binds all neurotrophins with similar affinity. For elucidation of its function, mice bearing a null mutation in the locus were generated. Examination sympathetic innervation target tissues revealed that pineal glands lacked and sweat gland was absent or reduced particular footpads. absence adult reflects failure axons to reach these targets during development rather than deficit. These results indicate facilitates specific populations neurons, for...
The Cre/ lox P system is increasingly showing promise for investigating genes involved in neural function. Here, we demonstrate that vivo modification of the mouse brain can be accomplished a spatial- and temporal-specific manner by targeted delivery an adeno-associated virus (AAV) encoding green fluorescent protein/Cre recombinase (GFP/Cre) fusion protein. By using reporter mouse, which Cre activates β-galactosidase expression, long-term recombination neurons hippocampus, striatum, septum...
The makings of motor neuron disease Developing neurons link the muscles to central nervous system. Amin et al. found that microRNA-218 (miR-218) was expressed in developing and repressed a wide network genes whose expression typifies other sorts neurons. Mice lacking miR-218 died at birth with symptoms characteristic human diseases. Science , this issue p. 1525
Significance Opioid-induced respiratory depression (OIRD) is the direct cause of death from opioid overdose, which accounts for current global crisis. Here, we report that neurons expressing μ-opioid receptors in lateral parabrachial nucleus pontine group are necessary and sufficient pathogenesis OIRD. Activating these through endogenous or artificial G protein–coupled receptor signaling pathways rescues OIRD intact mice, suggesting its therapeutic utility patients.
Abstract Neuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution characterization of type diversity the brain 1 , neuronal often studied out context anatomical properties. To improve our understanding relationship between features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing link neural epigenomic...
Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, immediate avoidance. Yet little known about whether how multi-sensory cues are integrated conveyed each modality amygdala, a critical area perception learning. Here, we report neurons expressing calcitonin gene-related peptide (CGRP) in parvocellular...
Abstract Single-cell analyses parse the brain’s billions of neurons into thousands ‘cell-type’ clusters residing in different brain structures 1 . Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific types. Here we used epi-retro-seq 2 to link single-cell epigenomes and for 33,034 dissected from 32 regions projecting 24 targets (225 source-to-target combinations) across whole mouse brain. We highlight uses these data...
Mice lacking the low-affinity neurotrophin receptor p75 have multiple peripheral neural deficits. Here we examined developmental nature of these deficiencies. Peripheral axons in -/- embryos were severely stunted and poorly arborized from embryonic day 11.5 (E11.5) to E14.5. In vitro, neurite outgrowth dorsal root ganglia was significantly decreased at E12.5, suggesting that axonal growth embryo may result part defects elongation. Additionally, Schwann cell marker S100beta immunoreactivity...
We have generated a mouse where the clotting factor IX (FIX) gene has been disrupted by homologous recombination. The FIX nullizygous (-/-) was devoid of antigen in plasma. Consistent with bleeding disorder, coagulant activities for wild-type (+/+), heterozygous (+/-), and homozygous mice were 92%, 53%, <5%, respectively, activated partial thromboplastin time assays. Plasma activity deficient restored introducing murine via adenoviral vectors. Thus, these IX-deficient provide useful animal...
Corticotropin-releasing factor (CRF) receptor type 2beta (CRFR2beta) is expressed in the heart. Urocortin (Ucn)-I activation of CRFR2beta cardioprotective against ischemic reperfusion (I/R) injury by stimulation ERKs1/2 p42, 44. However, binding CRF 1, Ucn-I can also activate hypothalamic stress axis. Ucn-II/stresscopin related peptide and Ucn-III/stresscopin are two new members CRF/Ucn-I gene family selective for CRFR2beta. We propose that Ucn-II or Ucn-III will protect cardiomyocytes ex...
Corticotropin-releasing factor (CRF) and its paralogues urocortin (Ucn)I, -II, -III signal by activating their receptors, CRF receptors (CRFR)1 -2, to maintain homeostasis through endocrine, autonomic, behavioral responses. CRFR2 is found in cardiomyocytes endothelial smooth muscle cells of the systemic vasculature. Echocardiography cardiac catheterization were used mice assess physiologic effects i.v. UcnII deficiency on left ventricular function treatment augmented heart rate, exhibited...
ABSTRACT Postnatal homozygous neurotrophin-3 mutant mice display a loss of about half the sympathetic superior cervical ganglion (SCG) neurons (Ernfors, P., Lee, K.-F., Kucera, J. and Jaenisch, R. (1994a) Cell 77, 503-512; Farinas, I., Jones, K. R., Backus, C., Wang, X. Y. Reichardt, L. F. (1994) Nature 369, 658-661). We found that this is caused by excessive apoptosis neuroblasts leading to failure generate normal number during neurogenesis. NT-3 was also be required postnatally. In Nt-3−/−...
Urocortin 3 (Ucn 3), a member of the corticotropin-releasing factor (CRF) family peptides, is strongly expressed in mammalian pancreatic β cells and has been shown to stimulate insulin secretion. Here we report investigation hypothesis that endogenous Ucn regulates secretion, particularly presence nutrient excess. Secretion 3-like immunoreactivity from cultured was stimulated by high glucose secretagogs such as GLP-1; furthermore, 5 mRNA levels vivo were increased during positive energy...