Growth Cone Tctp Is Dynamically Regulated by Guidance Cues

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Translationally controlled tumor protein (Tctp) is implicated in retinal circuitry formation and axon development.
• Tctp transcripts are highly enriched in the axonal compartment of retinal ganglion cells (RGCs), suggesting local regulation is important.
• The specific role of axonal Tctp in axon development programs remains unclear.

Purpose of the Study:

• To investigate the regulation of Tctp levels in RGC growth cones by guidance cues.
• To determine the necessity of locally synthesized Tctp for retinal axon growth and guidance in vivo.

Main Methods:

• Utilized live imaging and translation reporters to monitor Tctp synthesis in growth cones.
• Examined Tctp level changes in response to Netrin-1 and Ephrin-A1.
• Assessed the impact of inhibiting de novo Tctp synthesis on retinal projections in vivo.

Main Results:

• Growth cone Tctp levels dynamically changed in response to Netrin-1 (increasing, dependent on protein synthesis and mTORC1) and Ephrin-A1 (decreasing, an mTORC1 inhibitor).
• Netrin-1-induced Tctp synthesis in growth cones is mediated by a specific 3'UTR mRNA isoform.
• Acute inhibition of de novo Tctp synthesis in axons did not affect retinal projection advancement in vivo.

Conclusions:

• Tctp levels in RGC growth cones are rapidly and oppositely regulated by guidance cues Netrin-1 and Ephrin-A1.
• Local Tctp synthesis in axons is not required for normal retinal axon growth and guidance during development.