Retrograde Ret signaling controls sensory pioneer axon outgrowth

Adam Tuttle, Catherine M. Drerup, Molly Marra, Hillary McGraw, Alex Nechiporuk

Research output: Contribution to journalArticle

Abstract

The trafficking mechanisms and transcriptional targets downstream of long-range neurotrophic factor ligand/receptor signaling that promote axon growth are incompletely understood. Zebrafish carrying a null mutation in a neurotrophic factor receptor, Ret, displayed defects in peripheral sensory axon growth cone morphology and dynamics. Ret receptor was highly enriched in sensory pioneer neurons and Ret51 isoform was required for pioneer axon outgrowth. Loss-of-function of a cargo adaptor, Jip3, partially phenocopied Ret axonal defects, led to accumulation of activated Ret in pioneer growth cones, and reduced retrograde Ret51 transport. Jip3 and Ret51 were also retrogradely co-transported, ultimately suggesting Jip3 is a retrograde adapter of active Ret51. Finally, loss of Ret reduced transcription and growth cone localization of Myosin-X, an initiator of filopodial formation. These results show a specific role for Ret51 in pioneer axon growth, and suggest a critical role for long-range retrograde Ret signaling in regulating growth cone dynamics through downstream transcriptional changes.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Sep 2 2019

Fingerprint

Growth Cones
Nerve Growth Factor Receptors
Axons
Cones
Zebrafish
Sensory Receptor Cells
Myosins
Growth
Defects
Protein Isoforms
Nerve Growth Factors
Transcription
Ligands
Mutation
Neurons
Neuronal Outgrowth

Keywords

  • axon growth
  • axonal transport
  • developmental biology
  • growth cone
  • lateral line
  • neuroscience
  • pioneer neuron
  • Ret
  • zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Retrograde Ret signaling controls sensory pioneer axon outgrowth. / Tuttle, Adam; Drerup, Catherine M.; Marra, Molly; McGraw, Hillary; Nechiporuk, Alex.

In: eLife, Vol. 8, 02.09.2019.

Research output: Contribution to journalArticle

Tuttle, Adam ; Drerup, Catherine M. ; Marra, Molly ; McGraw, Hillary ; Nechiporuk, Alex. / Retrograde Ret signaling controls sensory pioneer axon outgrowth. In: eLife. 2019 ; Vol. 8.
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