A5038178720- Single-cell and spatial transcriptomics
- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- RNA Research and Splicing
- Nerve injury and regeneration
- Nicotinic Acetylcholine Receptors Study
- Neurobiology and Insect Physiology Research
- Gene Regulatory Network Analysis
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Neural dynamics and brain function
- Muscle Physiology and Disorders
- Cholinesterase and Neurodegenerative Diseases
- Signaling Pathways in Disease
- Axon Guidance and Neuronal Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Alzheimer's disease research and treatments
- MicroRNA in disease regulation
- Adipose Tissue and Metabolism
- Neurogenetic and Muscular Disorders Research
Salk Institute for Biological Studies
2003-2023
Biochemical and genetic studies place the amyloid precursor protein (APP) at center stage of Alzheimer's disease (AD) pathogenesis. Although mutations in APP gene lead to dominant inheritance familial AD, normal function remains elusive. Here, we report that family proteins plays an essential role development neuromuscular synapses. Mice deficient its homolog APP-like 2 ( APLP2 ) exhibit aberrant apposition presynaptic marker with postsynaptic acetylcholine receptors excessive nerve terminal...
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
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...
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...
In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous nerve-evoked postsynaptic potentials in muscle die at birth. mutant embryos, abnormally increased nerve branching occurs on contact with muscle, hyperinnervation continues throughout subsequent prenatal development. Postsynaptically, ACh receptor clusters...
ABSTRACT We report the generation of a multimodal cell census and atlas mammalian primary motor cortex (MOp or M1) as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties, cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance...
Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates development of neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar blocking biosynthesis, eliminating postsynaptic increased motor axon branching and expanded innervation territory, suggesting synaptic growth AChRs. However, in contrast agrin-deficient mice...
Highlights•The p75 neurotrophin receptor interacts with Ret and GFRα co-receptors•p75 enhances GFL signaling by modulating the level of on cell surface•Loss leads to defects in GFL-mediated survival Ret-expressing neurons vitro•p75 is required for postnatal diversification nonpeptidergic nociceptorsSummaryProducing neuronal diversity adequately discriminate all elements somatosensation a complex task during organogenesis. The mechanisms guiding this process dorsal root ganglion (DRG) sensory...
Glial cells regulate multiple aspects of synaptogenesis. In the absence Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using genetic approach, we show that neural activity-regulated negative factors produced by drive neurodegeneration in cell-deficient mice. We find thrombin, hepatic serine protease central to hemostatic coagulation cascade, is one such factor. Trancriptomic analysis shows expression antithrombins serpin C1 and D1...
Summary Neuronal cell types are classically defined by their molecular properties, anatomy, and functions. While recent advances in single-cell genomics have led to high-resolution characterization of type diversity the brain, neuronal often studied out context anatomical properties. To better understand relationship between features defining cortical neurons, we combined retrograde labeling with single-nucleus DNA methylation sequencing link epigenomic properties projections. We examined...
Abstract Single-cell genetic and epigenetic analyses parse the brain’s billions of neurons into thousands “cell-type” clusters, each residing in different brain structures. Many these cell types mediate their unique functions by virtue targeted long-distance axonal projections to allow interactions between specific types. Here we have used Epi-Retro-Seq link single epigenomes associated for 33,034 dissected from 32 source regions projecting 24 targets (225 →target combinations) across whole...