Abstract
BackgroundPrevious studies have suggested that the axon guidance proteins Slit1 and Slit2 co-operate to establish the optic chiasm in its correct position at the ventral diencephalic midline. This is based on the observation that, although both Slit1 and Slit2 are expressed around the ventral midline, mice defective in either gene alone exhibit few or no axon guidance defects at the optic chiasm whereas embryos lacking both Slit1 and Slit2 develop a large additional chiasm anterior to the chiasm’s normal position. Here we used steerable-filters to quantify key properties of the population of axons at the chiasm in wild-type, Slit1−/−, Slit2−/− and Slit1−/−Slit2−/− embryos.ResultsWe applied the steerable-filter algorithm successfully to images of embryonic retinal axons labelled from a single eye shortly after they have crossed the midline. We combined data from multiple embryos of the same genotype and made statistical comparisons of axonal distributions, orientations and curvatures between genotype groups. We compared data from the analysis of axons with data on the expression of Slit1 and Slit2. The results showed a misorientation and a corresponding anterior shift in the position of many axons at the chiasm of both Slit2−/− and Slit1−/−Slit2−/− mutants. There were very few axon defects at the chiasm of Slit1−/− mutants.ConclusionsWe found defects of the chiasms of Slit1−/−Slit2−/− and Slit1−/− mutants similar to those reported previously. In addition, we discovered previously unreported defects resulting from loss of Slit2 alone. This indicates the value of a quantitative approach to complex pathway analysis and shows that Slit2 can act alone to control aspects of retinal axon routing across the ventral diencephalic midline.
Highlights
Previous studies have suggested that the axon guidance proteins Slit1 and Slit2 co-operate to establish the optic chiasm in its correct position at the ventral diencephalic midline
Retinal ganglion cell (RGC) axons from the two eyes converge on each other at the midline of the ventral part of the brain where they either cross the midline or turn away from it, forming the ×-shaped optic chiasm. The formation of this pathway is achieved through the growth of RGC axons that exit the retina in tight bundles to reach the midline at a position ventral to the hypothalamus, where they either cross or do not cross depending on the retinal locations of their cell bodies
Guidance molecules that have been implicated in these regulatory tasks include Shh, which acts as a midline repellent to RGC axons except at the point where the chiasm forms [1], EphrinB2 and its receptor EphB1, which are critical for ipsilateral/contralateral sorting [2], and the extracellular secreted molecules Slit1 and Slit2, which signal via Robo receptors to constrain axons to the region of the chiasm [3,4,5,6]
Summary
Previous studies have suggested that the axon guidance proteins Slit and Slit co-operate to establish the optic chiasm in its correct position at the ventral diencephalic midline. Growing axons are guided at their distal tips by growth cones, which move using relatively autonomous mechanisms to sense and respond to environmental cues Some of these cues are molecules distributed in gradients that either attract specific growth cones up their concentration gradients (chemoattractants) or repel growth cones away from their sites of increasing concentrations (chemorepellents). One. Retinal ganglion cell (RGC) axons from the two eyes converge on each other at the midline of the ventral part of the brain (ventral to the hypothalamus) where they either cross the midline (the contralateral tract) or turn away from it (the ipsilateral tract), forming the ×-shaped optic chiasm. Guidance molecules that have been implicated in these regulatory tasks include Shh, which acts as a midline repellent to RGC axons except at the point where the chiasm forms [1], EphrinB2 and its receptor EphB1, which are critical for ipsilateral/contralateral sorting [2], and the extracellular secreted molecules Slit and Slit, which signal via Robo receptors to constrain axons to the region of the chiasm [3,4,5,6]
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