A compartmentalized microfluidic neuromuscular co-culture system reveals spatial aspects of GDNF functions

Eitan Erez Zahavi, Ariel Ionescu, Shani Gluska, Tal Gradus, Keren Ben-Yaakov, Eran Perlson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1241-1252
Number of pages12
JournalJournal of Cell Science
Volume128
Issue number6
DOIs
StatePublished - 2015

Keywords

  • Axon degeneration
  • Axonal transport
  • GDNF
  • Microfluidic chamber
  • Neuromuscular junction
  • Neurotrophic factors

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