A. E. Renton, A. Chiò, and B. J. Traynor, State of play in amyotrophic lateral sclerosis genetics, Nature Neuroscience, vol.67, issue.1, pp.17-23, 2014.
DOI : 10.1002/ana.22611

G. Bensimon, L. Lacomblez, and V. Meininger, A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis, New England Journal of Medicine, vol.330, issue.9, pp.585-591, 1994.
DOI : 10.1056/NEJM199403033300901

L. Poppe, L. Rué, W. Robberecht, . Van-den, and L. Bosch, Translating biological findings into new treatment strategies for amyotrophic lateral sclerosis (ALS), Experimental Neurology, vol.262
DOI : 10.1016/j.expneurol.2014.07.001

URL : https://doi.org/10.1016/j.expneurol.2014.07.001

M. Arbab, S. Baars, and N. Geijsen, Modeling motor neuron disease: the matter of time, Trends in Neurosciences, vol.37, issue.11, pp.642-652, 2014.
DOI : 10.1016/j.tins.2014.07.008

N. A. Lanson and U. B. Pandey, FUS-related proteinopathies: Lessons from animal models, Brain Research, vol.1462, pp.44-60, 2012.
DOI : 10.1016/j.brainres.2012.01.039

T. J. Kwiatkowski, Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis, Science, vol.18, issue.10, pp.1205-1208, 2009.
DOI : 10.1074/jbc.M705306200

C. Vance, Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6, Science, vol.31, issue.23, pp.1208-1211, 2009.
DOI : 10.1146/annurev.neuro.31.061307.090711

|. Doi, 10.1038/s41467-017-00911-y ARTICLE, NATURE COMMUNICATIONS NATURE COMMUNICATIONS |, vol.8
URL : https://hal.archives-ouvertes.fr/in2p3-00652853

D. Dormann and C. Haass, Fused in sarcoma (FUS): An oncogene goes awry in neurodegeneration, Molecular and Cellular Neuroscience, vol.56, pp.475-486, 2013.
DOI : 10.1016/j.mcn.2013.03.006

S. Lattante, G. A. Rouleau, and E. Kabashi, Mutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update, Human Mutation, vol.34, issue.Suppl 1, pp.812-826, 2013.
DOI : 10.1016/j.neurobiolaging.2012.09.005

X. Liu, The fused in sarcoma protein forms cytoplasmic aggregates in motor neurons derived from integration-free induced pluripotent stem cells generated from a patient with familial amyotrophic lateral sclerosis carrying the FUS-P525L mutation, neurogenetics, vol.25, issue.17, pp.223-231, 2015.
DOI : 10.1091/mbc.E14-05-1007

M. L. Liu, T. Zang, and C. L. Zhang, Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients, Cell Reports, vol.14, issue.1, pp.115-128, 2016.
DOI : 10.1016/j.celrep.2015.12.018

N. Ichiyanagi, Establishment of In??Vitro FUS-Associated Familial Amyotrophic Lateral Sclerosis Model Using Human Induced Pluripotent Stem Cells, Stem Cell Reports, vol.6, issue.4, pp.496-510, 2016.
DOI : 10.1016/j.stemcr.2016.02.011

M. Naujock, 4-Aminopyridine Induced Activity Rescues Hypoexcitable Motor Neurons from Amyotrophic Lateral Sclerosis Patient-Derived Induced Pluripotent Stem Cells, STEM CELLS, vol.33, issue.6, pp.1563-1575, 2016.
DOI : 10.1124/mol.108.050831

URL : http://onlinelibrary.wiley.com/doi/10.1002/stem.2354/pdf

B. J. Wainger, Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons, Cell Reports, vol.7, issue.1, pp.1-11, 2014.
DOI : 10.1016/j.celrep.2014.03.019

A. Devlin, Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability, Nature Communications, vol.6, pp.1-12, 2014.
DOI : 10.1186/1750-1326-6-73

URL : http://www.nature.com/articles/ncomms6999.pdf

L. R. Fischer, Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man, Experimental Neurology, vol.185, issue.2, pp.232-240, 2004.
DOI : 10.1016/j.expneurol.2003.10.004

K. R. Baldwin, V. K. Godena, V. L. Hewitt, and A. J. Whitworth, Axonal transport defects are a common phenotype in Drosophila models of ALS, Hum. Mol. Genet, vol.25, pp.2378-2392, 2016.

D. Vos, K. J. Hafezparast, and M. , Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?, Neurobiology of Disease, vol.105, pp.283-299, 2017.
DOI : 10.1016/j.nbd.2017.02.004

S. Paillusson, There's Something Wrong with my MAM; the ER???Mitochondria Axis and Neurodegenerative Diseases, Trends in Neurosciences, vol.39, issue.3, pp.146-157, 2016.
DOI : 10.1016/j.tins.2016.01.008

URL : https://doi.org/10.1016/j.tins.2016.01.008

A. Raturi and T. Simmen, Where the endoplasmic reticulum and the mitochondrion tie the knot: The mitochondria-associated membrane (MAM), Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol.1833, issue.1, pp.213-224, 2013.
DOI : 10.1016/j.bbamcr.2012.04.013

R. Stoica, ER???mitochondria associations are regulated by the VAPB???PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43, Nature Communications, vol.150, p.3996, 2014.
DOI : 10.1083/jcb.150.1.165

URL : http://www.nature.com/articles/ncomms4996.pdf

R. Stoica, ALS/FTD???associated FUS activates GSK???3?? to disrupt the VAPB???PTPIP51 interaction and ER???mitochondria associations, EMBO reports, vol.17, issue.9, pp.1326-1342, 2016.
DOI : 10.15252/embr.201541726

URL : http://embor.embopress.org/content/embor/17/9/1326.full.pdf

C. D-'ydewalle, HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1???induced Charcot-Marie-Tooth disease, Nature Medicine, vol.594, issue.8, pp.968-974, 2011.
DOI : 10.1152/ajpgi.00283.2003

C. Hubbert, HDAC6 is a microtubule-associated deacetylase, Nature, vol.250, issue.6887, pp.455-458, 2002.
DOI : 10.1006/excr.1999.4511

R. Sainath and G. Gallo, The dynein inhibitor Ciliobrevin D inhibits the bidirectional transport of organelles along sensory axons and impairs NGF-mediated regulation of growth cones and axon branches, Developmental Neurobiology, vol.14, issue.Part 17):, pp.757-777, 2014.
DOI : 10.1083/jcb.141.2.431

N. A. Reed, Microtubule Acetylation Promotes Kinesin-1 Binding and Transport, Current Biology, vol.16, issue.21, pp.2166-2172, 2006.
DOI : 10.1016/j.cub.2006.09.014

URL : https://doi.org/10.1016/j.cub.2006.09.014

I. Taes, Hdac6 deletion delays disease progression in the SOD1 G93A mouse model of, Hum. Mol. Genet, vol.22, pp.1-23, 2013.

S. H. Kim, N. P. Shanware, M. J. Bowler, and R. S. Tibbetts, Amyotrophic Lateral Sclerosis-associated Proteins TDP-43 and FUS/TLS Function in a Common Biochemical Complex to Co-regulate HDAC6 mRNA, Journal of Biological Chemistry, vol.447, issue.44, pp.34097-34105, 2010.
DOI : 10.1093/nar/gkp013

F. C. Fiesel, Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6, The EMBO Journal, vol.8, issue.1, pp.209-221, 2010.
DOI : 10.1074/jbc.M800342200

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808372/pdf

K. Miskiewicz, HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release, Cell Reports, vol.8, issue.1, pp.94-102, 2014.
DOI : 10.1016/j.celrep.2014.05.051

URL : https://doi.org/10.1016/j.celrep.2014.05.051

D. Bäumer, Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations, Neurology, vol.75, issue.7, pp.611-618, 2010.
DOI : 10.1212/WNL.0b013e3181ed9cde

Y. Maury, Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes, Nature Biotechnology, vol.480, issue.1, pp.89-96, 2014.
DOI : 10.1523/JNEUROSCI.4176-11.2012

URL : https://hal.archives-ouvertes.fr/hal-01115630

E. Kiskinis, Pathways Disrupted in Human ALS Motor Neurons Identified through Genetic Correction of Mutant SOD1, Cell Stem Cell, vol.14, issue.6, pp.781-795, 2014.
DOI : 10.1016/j.stem.2014.03.004

L. Ordovás, Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition, Stem Cell Reports, vol.5, issue.5, pp.918-931, 2015.
DOI : 10.1016/j.stemcr.2015.09.004

L. Ordovás, Rapid and Efficient Generation of Recombinant Human Pluripotent Stem Cells by Recombinase-mediated Cassette Exchange in the <em>AAVS1</em> Locus, Journal of Visualized Experiments, vol.117, issue.117, p.54718, 2016.
DOI : 10.3791/54718

T. A. Lagace and N. D. Ridgway, The role of phospholipids in the biological activity and structure of the endoplasmic reticulum, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol.1833, issue.11, pp.2499-2510, 2013.
DOI : 10.1016/j.bbamcr.2013.05.018

B. Kornmann, An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen, Science, vol.163, issue.3, pp.477-481, 2009.
DOI : 10.1083/jcb.200304040

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933203/pdf

J. R. Friedman, B. M. Webster, D. N. Mastronarde, K. J. Verhey, and G. K. Voeltz, ER sliding dynamics and ER???mitochondrial contacts occur on acetylated microtubules, The Journal of Cell Biology, vol.23, issue.3, pp.363-375, 2010.
DOI : 10.1242/jcs.041962

URL : http://jcb.rupress.org/content/jcb/190/3/363.full.pdf

K. V. Butler, Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A, Journal of the American Chemical Society, vol.132, issue.31, pp.10842-10846, 2010.
DOI : 10.1021/ja102758v

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916045/pdf

T. Majid, D. Griffin, Z. Criss, M. Jarpe, and R. G. Pautler, Pharmocologic treatment with histone deacetylase 6 inhibitor (ACY-738) recovers Alzheimer's disease phenotype in amyloid precursor protein, PS1) mice

T. Shelkovnikova, Modelling FUSopathies: focus on protein aggregation: Figure 1, Biochemical Society Transactions, vol.41, issue.6, pp.1613-1617, 2013.
DOI : 10.1042/BST20130212

URL : http://www.biochemsoctrans.org/content/ppbiost/41/6/1613.full.pdf

B. Wolozin, Regulated protein aggregation: stress granules and neurodegeneration, Molecular Neurodegeneration, vol.7, issue.1, p.56, 2012.
DOI : 10.1007/s00401-008-0480-1

URL : https://molecularneurodegeneration.biomedcentral.com/track/pdf/10.1186/1750-1326-7-56?site=molecularneurodegeneration.biomedcentral.com

T. L. Williamson and D. W. Cleveland, Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons, Nat. Neurosci, vol.2, pp.50-56, 1999.

B. Zhang, P. H. Tu, F. Abtahian, J. Q. Trojanowski, and V. M. Lee, Neurofilaments and Orthograde Transport Are Reduced in Ventral Root Axons of Transgenic Mice that Express Human SOD1 with a G93A Mutation, The Journal of Cell Biology, vol.76, issue.5, pp.1307-1315, 1997.
DOI : 10.1016/0092-8674(93)90157-L

A. F. Macaskill and J. Kittler, Control of mitochondrial transport and localization in neurons, Trends in Cell Biology, vol.20, issue.2, pp.102-112, 2010.
DOI : 10.1016/j.tcb.2009.11.002

E. J. Groen, ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN, Human Molecular Genetics, vol.22, issue.18, pp.3690-3704, 2013.
DOI : 10.1093/hmg/ddt222

A. Sharma, ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function, Nature Communications, vol.1, p.10465, 2016.
DOI : 10.1038/nprot.2011.439

URL : http://www.nature.com/articles/ncomms10465.pdf

W. Wang, Motor-Coordinative and Cognitive Dysfunction Caused by Mutant TDP-43 Could Be Reversed by Inhibiting Its Mitochondrial Localization, Molecular Therapy, vol.25, issue.1, pp.127-139, 2017.
DOI : 10.1016/j.ymthe.2016.10.013

H. Chen, Modeling ALS with iPSCs Reveals that Mutant SOD1 Misregulates Neurofilament Balance in Motor Neurons, Cell Stem Cell, vol.14, issue.6, pp.796-809, 2014.
DOI : 10.1016/j.stem.2014.02.004

URL : https://doi.org/10.1016/j.stem.2014.02.004

J. I. Hoell, RNA targets of wild-type and mutant FET family proteins, Nature Structural & Molecular Biology, vol.30, issue.12, pp.1428-1431, 2011.
DOI : 10.1111/j.1440-1789.2009.01088.x

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230689/pdf

A. F. Macaskill, Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at Synapses, Neuron, vol.61, issue.4, pp.541-555, 2009.
DOI : 10.1016/j.neuron.2009.01.030

V. K. Godena, Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations, Nature Communications, vol.44, p.5245, 2014.
DOI : 10.1016/j.cub.2005.07.064

URL : http://www.nature.com/articles/ncomms6245.pdf

K. J. Falkenberg and R. W. Johnstone, Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders, Nature Reviews Drug Discovery, vol.405, issue.9, pp.673-691, 2014.
DOI : 10.1016/j.virol.2010.06.001

URL : http://www.nature.com/nrd/journal/v14/n3/pdf/nrd4579.pdf

P. Vanden-berghe, G. W. Hennig, and T. K. Smith, Characteristics of intermittent mitochondrial transport in guinea pig enteric nerve fibers, AJP: Gastrointestinal and Liver Physiology, vol.286, issue.4, pp.671-682, 2004.
DOI : 10.1152/ajpgi.00283.2003

O. Urwyler, Investigating CNS synaptogenesis at single-synapse resolution by combining reverse genetics with correlative light and electron microscopy, Development, vol.142, issue.2, pp.394-405, 2015.
DOI : 10.1242/dev.115071

URL : http://dev.biologists.org/content/develop/142/2/394.full.pdf

W. G. Author, planned and performed most of the experiments. M.N. planned and performed the patch clamp measurements. L.F. helped with the iPSC differentiations and organized the schematic graph of MN differentiation. P.B. provided support for the electron microscopy experiments

A. P. , M. W. Th, W. V. Helped-with-the-ipsc-technology, P. V. , S. P. et al., helped with the axonal transport measurements and P.V.B. wrote the axonal transport analysis software. M.J. provided ACY-738. T.T. and N.G. provided technical support, Jo.S. helped with the images and Ti.V. was involved in the ASO experiments. P.V.D. provided fibroblasts and ideas for the project, F.W. and S.P. supervised part of the iPSC differentiation and the patch clamp recordings of motor neurons, Ja. S contributed to the additional iPSC control lines in the patch clamp recordings