title: Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons.
abstract: A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.
authors.affiliation: Laboratory for Neurodegenerative Diseases and Personalized Medicine, Department of Cell Research and Immunology, The Sagol School of Neurosciences, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Abashidze
authors.affiliation: Laboratory for Neurodegenerative Diseases and Personalized Medicine, Department of Cell Research and Immunology, The Sagol School of Neurosciences, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Veronica
authors.initials: V
authors.lastname: Gold
authors.affiliation: Department of Applied Mathematics, School of Mathematical Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Anavi
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Hayit
authors.initials: H
authors.lastname: Greenspan
authors.affiliation: Laboratory for Neurodegenerative Diseases and Personalized Medicine, Department of Cell Research and Immunology, The Sagol School of Neurosciences, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Miguel
authors.initials: M
authors.lastname: Weil
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004398:Dyneins / Q000378:metabolism; D004402:Dysautonomia, Familial / Q000235:genetics / Q000473:pathology; D005727:Ganglia, Spinal / Q000166:cytology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017933:Peripheral Nervous System / Q000254:growth & development / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D034741:RNA, Small Interfering; D014404:Tubulin; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; D004398:Dyneins