| First Author | Bush JR | Year | 2010 |
| Journal | Genesis | Volume | 48 |
| Issue | 9 | Pages | 540-53 |
| PubMed ID | 20665884 | Mgi Jnum | J:164695 |
| Mgi Id | MGI:4834974 | Doi | 10.1002/dvg.20658 |
| Citation | Bush JR, et al. (2010) Loss of Necdin impairs myosin activation and delays cell polarization. Genesis 48(9):540-53 |
| abstractText | 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. |
