Potential role of Pax-2 in retinal axon navigation through the chick optic nerve stalk and optic chiasm

The degree of fiber decussation at the optic chiasm differs between species, ranging from complete crossing in lower vertebrates to highly complex patterns of intermingling of the fibers from the two eyes seen in mammals and birds. Understanding the genetic control of fiber guidance through the chiasm is therefore important to unravel the developmental mechanisms within the visual system. Here we first report on early stages of chiasm formation, with pioneering axons from the left eye consistently arriving earlier than their counterparts from the right eye. This initial left-right asymmetry is transient and no functional significance is assigned to it yet. Secondly, we examined formation of the chiasm in relation with the expression of the transcription factor Pax-2 along the ventral eye cup and optic nerve stalk. Finally, in order to examine causal involvement of Pax-2 in chiasm formation, the gene was overexpressed along the neuraxis and in the eye cup at embryonic stages preceding the exit of axons from the eye, and hence arrival of axons at the chiasm. When studied with neuroanatomical tracing, Pax-2 overexpression resulted in visibly anomalous decussation of axons at the chiasm. A likely consequence of this perturbation was erroneous arrival of axons at the tectum, as observed by anterograde staining from the retina. These data suggest that balanced expression of Pax-2 results in the correct formation of the chick chiasm at early stages by imposing accurate pathfinding within the optic stalk and the midline.