Reference - Detail
| RRC ID | 10914 |
|---|---|
| Author | Bush JR, Wevrick R. |
| Title | Loss of Necdin impairs myosin activation and delays cell polarization. |
| Journal | Genesis |
| Abstract |
NDN is one of several genes inactivated in Prader-Willi syndrome (PWS), a developmental disorder characterized by obesity, hypotonia, and developmental delay. We demonstrate that loss of Necdin in murine and human fibroblasts impairs polarity initiation through a Cdc42-myosin-dependent pathway, thereby reducing cell migration. We identified defective polarization in both primary neuron cultures and in the developing limb in Ndn-null mice. Ndn-null neurons fail to activate myosin light chain and display defective polarization with respect to a brain-derived neurotrophic factor gradient. Pax3+ muscle progenitors in Ndn-null developing forelimbs display defective polarization, do not adequately migrate into the dorsal limb bud, and extensor muscles are consequently smaller. These results provide strong evidence that Necdin is a key protein regulating polarization of the cytoskeleton during development. Furthermore, this is the first demonstration of a cellular defect in PWS and suggests a novel molecular mechanism to explain neurological and muscular pathophysiologies in PWS. |
| Volume | 48(9) |
| Pages | 540-53 |
| Published | 2010-9-1 |
| DOI | 10.1002/dvg.20658 |
| PMID | 20665884 |
| MeSH | Animals Cell Movement / physiology* Cell Polarity / physiology* Cytoskeleton / physiology* Fibroblasts Humans Immunoblotting Immunohistochemistry Limb Buds / physiology Mice Myosins / metabolism Nerve Tissue Proteins / deficiency* Nerve Tissue Proteins / metabolism Neurons / physiology Nuclear Proteins / deficiency* Nuclear Proteins / metabolism Phosphorylation Prader-Willi Syndrome / genetics Prader-Willi Syndrome / metabolism Prader-Willi Syndrome / physiopathology* Signal Transduction / genetics Signal Transduction / physiology* cdc42 GTP-Binding Protein / metabolism |
| IF | 1.76 |
| Times Cited | 11 |
| WOS Category | GENETICS & HEREDITY DEVELOPMENTAL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Resource | |
| Human and Animal Cells | PWS-Yamaguchi(RCB1560) |