title: Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects.
abstract: Some mutations of the LRRK2 gene underlie autosomal dominant form of Parkinson's disease (PD). The G2019S is a common mutation that accounts for about 2% of PD cases. To understand the pathophysiology of this mutation and its possible developmental implications, we developed an in vitro assay to model PD with human induced pluripotent stem cells (hiPSCs) reprogrammed from skin fibroblasts of PD patients suffering from the LRKK2 G2019S mutation. We differentiated the hiPSCs into neural stem cells (NSCs) and further into dopaminergic neurons. Here we show that NSCs bearing the mutation tend to differentiate less efficiently into dopaminergic neurons and that the latter exhibit significant branching defects as compared to their controls.
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Borgs
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Elise
authors.initials: E
authors.lastname: Peyre
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Alix
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hanon
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Grobarczyk
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Juliette D
authors.initials: JD
authors.lastname: Godin
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Purnelle
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Krusy
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.|Service de Neurologie, CHU Sart Tilman, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Maquet
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.|Service d'othorhinolaryngologie, CHU Sart Tilman, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Seutin
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
authors.affiliation: GIGA-Research, GIGA-Neurosciences, Université de Liège, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000201:enzymology*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology; D016501:Neurites / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics; D010641:Phenotype
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2