Zic2 patterns binocular vision by specifying the uncrossed retinal projection

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Neuronal subtype identity and axonal trajectory are controlled by transcription factors during CNS development.
• Genes regulating retinal ganglion cell (RGC) axon routing at the optic chiasm for binocular vision are largely unknown.

Purpose of the Study:

• To identify regulatory genes controlling RGC axon pathfinding at the optic chiasm.
• To investigate the role of Zic2 in RGC axon guidance and its evolutionary conservation.

Main Methods:

• Expression analysis of Zic2 in RGCs.
• Loss- and gain-of-function studies of Zic2 in RGCs.
• Comparative analysis of Zic2 expression across species.

Main Results:

• Zic2 is expressed in RGCs with uncrossed trajectories during development.
• Zic2 is necessary and sufficient for RGC axon repulsion at the optic chiasm midline.
• Zic2 expression levels correlate with binocularity across species, indicating conserved function.

Conclusions:

• Zic2 is a critical transcription factor for ipsilateral RGC axon guidance at the optic chiasm.
• Zic2 acts as a molecular determinant for RGCs projecting to the ipsilateral hemisphere.
• This study provides evidence for transcriptional control of axon pathfinding at the midline.