Nerve growth factor promotes reorganization of the axonal microtubule array at sites of axon collateral branching

Andrea Ketschek, Steven Jones, Mirela Spillane, Farida Korobova, Tatyana Svitkina, Gianluca Gallo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


The localized debundling of the axonal microtubule array and the entry of microtubules into axonal filopodia are two defining features of collateral branching. We report that nerve growth factor (NGF), a branch-inducing signal, increases the frequency of microtubule debundling along the axon shaft of chicken embryonic sensory neurons. Sites of debundling correlate strongly with the localized targeting of microtubules into filopodia. Platinum replica electron microscopy suggests physical interactions between debundled microtubules and axonal actin filaments. However, as evidenced by depolymerization of actin filaments and inhibition of myosin II, actomyosin force generation does not promote debundling. In contrast, loss of actin filaments or inhibition of myosin II activity promotes debundling, indicating that axonal actomyosin forces suppress debundling. MAP1B is a microtubule associated protein that represses axon branching. Following treatment with NGF, microtubules penetrating filopodia during the early stages of branching exhibited lower levels of associated MAP1B. NGF increased and decreased the levels of MAP1B phosphorylated at a GSK-3β site (pMAP1B) along the axon shaft and within axonal filopodia, respectively. The levels of MAP1B and pMAP1B were not altered at sites of debundling, relative to the rest of the axon. Unlike the previously determined effects of NGF on the axonal actin cytoskeleton, the effects of NGF on microtubule debundling were not affected by inhibition of protein synthesis. Collectively, these data indicate that NGF promotes localized axonal microtubule debundling, that actomyosin forces antagonize microtubule debundling, and that NGF regulates pMAP1B in axonal filopodia during the early stages of collateral branch formation.

Original languageEnglish (US)
Pages (from-to)1441-1461
Number of pages21
JournalDevelopmental Neurobiology
Issue number12
StatePublished - Dec 1 2015


  • Bundling
  • Consolidation
  • Contractility
  • Debundling
  • GSK-3β
  • Microtubule associated protein 1B
  • Myosin II
  • Splaying
  • Sprout
  • Sprouting
  • Transport

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience


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