title: Nestin is not essential for development of the CNS but required for dispersion of acetylcholine receptor clusters at the area of neuromuscular junctions.
abstract: Nestin is expressed in many different progenitors during development including those of the CNS, heart, skeletal muscle, and kidney. The adult expression is mainly restricted to the subependymal zone and dentate gyrus of the brain, the neuromuscular junction, and renal podocytes. In addition, this intermediate filament protein has served as a marker of neural stem/progenitor cells for close to 20 years. Therefore it is surprising that its function in development and adult physiology is still poorly understood. Here we report that nestin deficiency is compatible with normal development of the CNS. The mutant mice, however, show impaired motor coordination. Furthermore, we found that the number of acetylcholine receptor clusters, the nerve length, and the endplate bandwidth are significantly increased in neuromuscular junction area of nestin-deficient mice. This is similar to the phenotype described for deficiency of cyclin-dependent kinase 5 (Cdk5), a candidate downstream affecter of nestin. Moreover, we demonstrate that nestin deficiency can rescue maintenance of acetylcholine receptor clusters in the absence of agrin, similar to Cdk5/agrin double knock-outs, suggesting that the observed nestin deficiency phenotype is the consequence of aberrant Cdk5 activity.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5T 3H7 Canada.
authors.forename: Paria
authors.initials: P
authors.lastname: Mohseni
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Sung
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: Christine L
authors.initials: CL
authors.lastname: Laliberte
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Pallari
authors.forename: Mark
authors.initials: M
authors.lastname: Henkelman
authors.forename: John
authors.initials: J
authors.lastname: Georgiou
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.forename: Susan E
authors.initials: SE
authors.lastname: Quaggin
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thorner
authors.forename: John E
authors.initials: JE
authors.lastname: Eriksson
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
mesh_terms: D018171:Agrin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D018390:Gene Targeting / Q000379:methods; D007381:Intermediate Filament Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D064231:Nestin; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000502:physiology; D011940:Receptor Aggregation / Q000235:genetics / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D018171:Agrin; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011950:Receptors, Cholinergic; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse