TY - JOUR TI - Retrograde Ret signaling controls sensory pioneer axon outgrowth AU - Tuttle, Adam AU - Drerup, Catherine M AU - Marra, Molly AU - McGraw, Hillary AU - Nechiporuk, Alex V A2 - Tissir, Fadel A2 - Stainier, Didier Y VL - 8 PY - 2019 DA - 2019/09/02 SP - e46092 C1 - eLife 2019;8:e46092 DO - 10.7554/eLife.46092 UR - https://doi.org/10.7554/eLife.46092 AB - 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. KW - pioneer neuron KW - growth cone KW - lateral line KW - axon growth KW - Ret KW - axonal transport JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -