A5022760882- Hereditary Neurological Disorders
- RNA regulation and disease
- RNA Research and Splicing
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Neurological diseases and metabolism
- MicroRNA in disease regulation
- Plant Molecular Biology Research
- Genomics and Chromatin Dynamics
- Genetic Neurodegenerative Diseases
- Hippo pathway signaling and YAP/TAZ
- Signaling Pathways in Disease
- Estrogen and related hormone effects
- Cell Image Analysis Techniques
- Endoplasmic Reticulum Stress and Disease
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- Photosynthetic Processes and Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Peripheral Neuropathies and Disorders
- Lipid metabolism and biosynthesis
- Chromosomal and Genetic Variations
- Cholesterol and Lipid Metabolism
- Neurogenetic and Muscular Disorders Research
- Plant Reproductive Biology
Stanford University
2020-2021
Howard Hughes Medical Institute
2020-2021
John Wiley & Sons (United States)
2019
Hudson Institute
2019
University of Wisconsin–Madison
2011-2019
Myelin is formed by specialized myelinating glia: oligodendrocytes and Schwann cells in the central peripheral nervous systems, respectively. While there are distinct developmental aspects regulatory pathways these two cell types, myelination both systems requires transcriptional activator Sox10. Sox10 interacts with type-specific transcription factors at some loci to induce myelin gene expression, but it largely unknown how networks globally compare between cells. We used vivo ChIP-Seq...
Schwann cell differentiation and subsequent myelination of the peripheral nervous system require action several transcription factors, including Sox10, which is vital at multiple stages development. The transition from immature to myelinating also regulated posttranscriptionally depends upon Dicer-mediated processing microRNAs (miRNAs). Although specific miRNA targets have begun be identified, mechanisms establishing dynamic regulation expression not been elucidated. We performed profiling...
Objective Our goal was to define the genetic cause of profound hypomyelination in taiep rat model and determine its relevance human white matter disease. Methods Based on previous localization mutation chromosome 9, we tested whether resided within Tubb4a (β‐tubulin 4A) gene, because mutations TUBB4A gene have been described patients with central nervous system hypomyelination. To accumulation microtubules led progressive demyelination, analyzed spinal cord optic nerves 2‐year‐old rats by...
Schwann cells are myelinating glia in the peripheral nervous system that form myelin sheath. A major cause of neuropathy is a copy number variant involving Peripheral Myelin Protein 22 (PMP22) gene, which located within 1.4-Mb duplication on chromosome 17 associated with most common Charcot-Marie-Tooth Disease (CMT1A). Rodent models CMT1A have been used to show reducing Pmp22 overexpression mitigates several aspects CMT1A-related phenotype. Mechanistic studies regulation identified enhancers...
Successful myelination of the peripheral nervous system depends upon induction major protein components myelin, such as myelin 22 (PMP22). Myelin stability is also sensitive to levels PMP22, a 1.4 Mb duplication on human chromosome 17, resulting in three copies most common cause neuropathy Charcot-Marie-Tooth disease. The transcription factor Egr2/Krox20 required for high level expression Pmp22 Schwann cells but its activation elements have not yet been determined. Using chromatin...
The early growth response (EGR) family of transcription factors has been implicated in control lipid biosynthetic genes. Egr1 is induced by insulin both vitro and vivo the most highly expressed member liver. In this study, we investigated whether regulates cholesterol genes Using an insulin-sensitive liver cell line, show that localization to treatment precedes induction Reduction expression using targeted siRNA blunted insulin-dependent A similar reduction squalene epoxidase was also...
The structural integrity of myelin formed by Schwann cells in the peripheral nervous system (PNS) is required for proper nerve conduction and dependent on adequate expression genes including protein 22 (PMP22). Consequently, excess PMP22 resulting from its genetic duplication overexpression has been directly associated with neuropathy called Charcot-Marie-Tooth disease type 1A (CMT1A), most prevalent CMT. Here, an attempt to identify transcriptional inhibitors therapeutic value toward CMT1A,...
Genetic modifiers in rare disease have long been suspected to contribute the considerable variance expression, including Charcot-Marie-Tooth type 1A (CMT1A). To address this question, Inherited Neuropathy Consortium collected a large standardized sample of such CMT1A patients over period 8 years. is caused most by uniformly sized 1.5 Mb duplication event involving gene PMP22.
Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate myelination. Here we ask if modulating NRG1 levels in neurons would restore myelination a model congenital hypomyelinating neuropathy (CHN). Using mouse CHN, improved defects by early overexpression III. Surprisingly, improvement was...
Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a uniform 1.5-Mb duplication on chromosome 17p, which includes the PMP22 gene. Patients often present classic neuropathy phenotype, but also with high clinical variability.
Schwann cells and oligodendrocytes are the myelinating of peripheral central nervous system, respectively. Despite having different myelin components transcription factors driving their terminal differentiation there shared molecular mechanisms between two. Sox10 is one common factor required for several steps in development glia. However, other divergent as need early growth response 2/Krox20 require Myrf. Likewise, some signaling pathways, like Erk1/2 kinases, necessary both cell types...
SUMMARY Dynamic cell states underlie flexible developmental programs, such as with the stomatal lineage of Arabidopsis epidermis. Initial stages feature asynchronous and indeterminate divisions modulated by environmental cues, enabling fate flexibility to generate requisite density pattern stomata for a given environment. It remains unclear, however, how fates is controlled. Here, we uncovered distinct models state differentiation within leaf tissue leveraging single-cell transcriptomics...
As next generation sequencing technologies are becoming more economical, large-scale ChIP-seq studies enabling the investigation of roles transcription factor binding and epigenome on phenotypic variation. Studying such variation requires individual level experiments. Standard designs for experiments employ a paired control per sample. Genomic coverage is often sacrificed to increase resources ChIP samples. However, quality ChIP-enriched regions identifiable from experiment depends...
The function of the peripheral nervous system is dependent on myelination nerves by Schwann cells. This process tightly governed a network transcription factors during development. Myelin stability adversely affected in most common form hereditary neuropathy called Charcot‐Marie‐Tooth Disease. form, classified as CMT1a, caused 1.4 Mb duplication chromosome 17. includes abundantly expressed myelin gene Peripheral Protein 22 ( Pmp22 ), which associated with multiple disease states...
Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from axonal protein neuregulin 1 type III regulate Schwann cell fate myelination. Here we ask if modulating levels in neurons would restore myelination a model congenital hypomyelinating neuropathy (CHN). Using mouse CHN, rescued defects by early overexpression III. Surprisingly, rescue was independent upregulation...