title: Necdin protects embryonic motoneurons from programmed cell death.
abstract: NECDIN belongs to the type II Melanoma Associated Antigen Gene Expression gene family and is located in the Prader-Willi Syndrome (PWS) critical region. Necdin-deficient mice develop symptoms of PWS, including a sensory and motor deficit. However, the mechanisms underlying the motor deficit remain elusive. Here, we show that the genetic ablation of Necdin, whose expression is restricted to post-mitotic neurons in the spinal cord during development, leads to a loss of 31% of specified motoneurons. The increased neuronal loss occurs during the period of naturally-occurring cell death and is not confined to specific pools of motoneurons. To better understand the role of Necdin during the period of programmed cell death of motoneurons we used embryonic spinal cord explants and primary motoneuron cultures from Necdin-deficient mice. Interestingly, while Necdin-deficient motoneurons present the same survival response to neurotrophic factors, we demonstrate that deletion of Necdin leads to an increased susceptibility of motoneurons to neurotrophic factor deprivation. We show that by neutralizing TNFα this increased susceptibility of Necdin-deficient motoneurons to trophic factor deprivation can be reduced to the normal level. We propose that Necdin is implicated through the TNF-receptor 1 pathway in the developmental death of motoneurons.
authors.affiliation: Inserm-Avenir, Mediterranean Institute of Neurobiology, INMED, Marseille, France.
authors.forename: Julianne
authors.initials: J
authors.lastname: Aebischer
authors.forename: Rachel
authors.initials: R
authors.lastname: Sturny
authors.forename: David
authors.initials: D
authors.lastname: Andrieu
authors.forename: Anne
authors.initials: A
authors.lastname: Rieusset
authors.forename: Fabienne
authors.initials: F
authors.lastname: Schaller
authors.forename: Sandrine
authors.initials: S
authors.lastname: Geib
authors.forename: Cédric
authors.initials: C
authors.lastname: Raoul
authors.forename: Françoise
authors.initials: F
authors.lastname: Muscatelli
mesh_terms: D000818:Animals; D017209:Apoptosis; D004622:Embryo, Mammalian; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006614:Hindlimb / Q000166:cytology; D006801:Humans; D008161:Lumbosacral Region / Q000473:pathology; D008297:Male; D051379:Mice; D008938:Mitosis / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011218:Prader-Willi Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; C069766:necdin