title: A compartmentalized microfluidic neuromuscular co-culture system reveals spatial aspects of GDNF functions.
abstract: Bidirectional molecular communication between the motoneuron and the muscle is vital for neuromuscular junction (NMJ) formation and maintenance. The molecular mechanisms underlying such communication are of keen interest and could provide new targets for intervention in motoneuron disease. Here, we developed a microfluidic platform with motoneuron cell bodies on one side and muscle cells on the other, connected by motor axons extending through microgrooves to form functional NMJs. Using this system, we were able to differentiate between the proximal and distal effects of oxidative stress and glial-derived neurotrophic factor (GDNF), demonstrating a dying-back degeneration and retrograde transmission of pro-survival signaling, respectively. Furthermore, we show that GDNF acts differently on motoneuron axons versus soma, promoting axonal growth and innervation only when applied locally to axons. Finally, we track for the first time the retrograde transport of secreted GDNF from muscle to neuron. Thus, our data suggests spatially distinct effects of GDNF--facilitating growth and muscle innervation at axon terminals and survival pathways in the soma.
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Eitan Erez
authors: EE
authors: Zahavi
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Ariel
authors: A
authors: Ionescu
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Shani
authors: S
authors: Gluska
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Tal
authors: T
authors: Gradus
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Keren
authors: K
authors: Ben-Yaakov
authors: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel eranpe@post.tau.ac.il.
authors: Eran
authors: E
authors: Perlson
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D044085:Microfluidics; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium
keywords: Axon degeneration; Axonal transport; GDNF; Microfluidic chamber; Neuromuscular junction; Neurotrophic factors
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