The role of Foxg1 in retinal axon divergence at the optic chiasm.

Abstract

During murine development, retinal ganglion cell (RGC) axons are presented with multiple navigational choices as they exit the eyes and follow a complex path to targets in the thalamus and superior colliculus of the brain. The optic chiasm is a major choice point, positioned at the ventral midline of the hypothalamus, where the majority of retinal axons cross to the contralateral side of the brain whilst only 3% remain uncrossed and project ipsilaterally. Identifying the cellular and molecular processes involved in retinal axon divergence at the chiasm is an intense area of study and knockout mice have proved useful tools. Foxg1 is a winged helix transcription factor that is expressed in the nasal retina, nasal optic stalk and anterior ventral hypothalamus, which are all structures that retinal axons encounter as they project out of the RGC layer towards the chiasm. The coincidence between the expression pattern of Foxg1 and the route followed by retinal axons led to the hypothesis that Foxg1 plays a role in guiding retinal axons at the optic chiasm. Previous experiments in this laboratory lent support to this idea by revealing an increase in the number of ipsilateral projections in Foxg1-/- mouse embryos from both nasal and temporal retina. Since Foxg1 is expressed in both the nasal retina and at the optic chiasm midline, the main hypotheses for this thesis are that Foxg1 influences retinal axon divergence by transcriptionally regulating the expression of cell surface molecules on (1) growth cones from the nasal retina or (2) guidance molecules on chiasm cells. In order to address these possibilities, the key aims of this thesis were (i) to investigate whether Foxg1 is primarily required in the nasal retina or at the chiasm for retinal axon divergence, (ii) to determine whether the Foxg1 null retina and chiasm are patterned differently from those of wild types and (iii) to investigate the expression of candidate molecules in the retina or chiasm known to influence retinal axon navigation.