R7 photoreceptor axon growth is temporally controlled by the transcription factor Ttk69, which inhibits growth in part by promoting transforming growth factor-β/activin signaling.
Work on axon growth has classically focused on understanding how extrinsic cues control growth cone dynamics independent of the cell body. However, more recently, neuron-intrinsic transcription factors have been shown to influence both normal and regenerative axon growth, suggesting that understanding their mechanism of action is of clinical importance. We are studying axon targeting in the Drosophila visual system and here show that the BTB/POZ zinc-finger transcription factor Tramtrack69 (Ttk69) plays an instructive role in inhibiting the growth of R7 photoreceptor axon terminals. Although ttk69 mutant R7 axons project to the correct medullar target layer, M6, their terminals fail to remain retinotopically restricted and instead grow laterally within M6. This overgrowth is not caused by an inability to be repelled by neighboring R7 axons or by an inability to recognize and initiate synapse formation with postsynaptic targets. The overgrowth is progressive and occurs even if contact between ttk69 mutant R7 axons and their normal target layer is disrupted. Ttk69 is first expressed in wild-type R7s after their axons have reached the medulla; ttk69 mutant R7 axon terminal overgrowth begins shortly after this time point. We find that expressing Ttk69 prematurely in R7s collapses their growth cones and disrupts axon extension, indicating that Ttk69 plays an instructive role in this process. A TGF-β/Activin pathway was shown previously to inhibit R7 axon terminal growth. We find that Ttk69 is required for normal activation of this pathway but that Ttk69 likely also inhibits R7 axon growth by a TGF-β/Activin-independent mechanism.
Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA.
Jonathan S
JS
Kniss
Scott
S
Holbrook
Tory G
TG
Herman
D028341:Activins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D029721:Drosophila Proteins; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; C075878:ttk protein, Drosophila; D028341:Activins