The transcription factor Engrailed-2 guides retinal axons

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Engrailed-2 (En-2) is a transcription factor crucial for midbrain development and optic tectum patterning.
• En-2's known function involves DNA binding, but it also possesses domains suggesting roles in cell communication.
• The optic tectum is a key target for topographic input from the retina.

Purpose of the Study:

• To investigate the potential role of Engrailed-2 (En-2) protein in guiding retinal axon growth cones.
• To determine if En-2 protein can directly influence axon pathfinding in the developing visual system.

Main Methods:

• Utilizing Xenopus as a model organism.
• Applying external gradients of En-2 protein to retinal axon growth cones.
• Employing fluorescently tagged En-2 to track its internalization into growth cones.
• Assessing axon turning responses in the presence of En-2 and protein synthesis inhibitors.

Main Results:

• External En-2 protein gradients differentially guide Xenopus retinal axon growth cones: repelling temporal axons and attracting nasal axons.
• Fluorescently tagged En-2 rapidly accumulates inside growth cones.
• A mutant En-2 form unable to enter cells does not induce axon turning.
• En-2 internalization triggers protein phosphorylation and local protein synthesis, essential for axon turning.
• Inhibitors of protein synthesis block En-2-mediated axon turning responses.

Conclusions:

• Engrailed-2 (En-2) protein acts as a guidance cue for retinal axons, influencing topographic map formation.
• En-2's guidance function depends on its internalization and ability to stimulate local protein synthesis within growth cones.
• These findings reveal a novel mechanism for En-2 in vertebrate visual system development and neural circuit assembly.