necdin protects embryonic motoneurons from programmed cell death从程序性细胞死亡necdin保护胚胎运动神经元.pdfVIP

Necdin Protects Embryonic Motoneurons from Programmed Cell Death Julianne Aebischer1,2, Rachel Sturny2,3, David Andrieu2,4, Anne Rieusset2,4, Fabienne Schaller2,4, 2,4 ´ 1,2 2,4 Sandrine Geib , Cedric Raoul , Franc¸oise Muscatelli * ´ ´ 1 Inserm-Avenir, Mediterranean Institute of Neurobiology, INMED, Marseille, France, 2 Universite d’Aix-Marseille, Faculte des Sciences, Marseille, France, 3 Developmental Biology Institute of Marseille Luminy, IBDML, Marseille, France, 4 Inserm U901, Mediterranean Institute of Neurobiology, INMED, Campus scientifique de Luminy, Marseille, France 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