RRC ID 10914
著者 Bush JR, Wevrick R.
タイトル Loss of Necdin impairs myosin activation and delays cell polarization.
ジャーナル 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.
巻・号 48(9)
ページ 540-53
公開日 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
引用数 11
WOS 分野 GENETICS & HEREDITY DEVELOPMENTAL BIOLOGY
リソース情報
ヒト・動物細胞 PWS-Yamaguchi(RCB1560)