Deciphering the roundabout code underlying postoptic commissure formation in the developing Zebrafish forebrain

During development, the formation of the nervous system requires the proper guidance of axons to their synaptic targets by environmental and secreted molecular cues. Neuronal guidance in bilateral organisms is further complicated by the existence of a midline. In order to functionally connect both hemispheres of the brain, axons must make the crucial decision to cross the midline, forming bundles of axons called commissures. The first commissural axons to cross during development in the Danio rerio model system are those that compose the post optic commissure (POC) in the diencephalon. These axons have been demonstrated to grow along a bridge-like structure composed of astroglial cells. Slits, a family of secreted guidance cues and their Roundabout (Robo) receptors have been implicated in the positioning of both the astroglial bridge and POC axons. Significantly, the four Robos (1-4) isoforms in zebrafish are differentially expressed in the POC astroglia and neurons. Adopting a loss of function approach using both morpholino knockdowns and mutant (robo3) analysis, we aim to determine the functions of Robos3variant1, 3variant2, and 4 in POC axonal and astroglial positioning. Current results suggest that Robo3var1 functions through Slit1a to position axons and glia. Robo3var2 does not appear to play a role in POC axon or glial cell organization. Additionally, Robo4 appears to be responsible for glial-axon interactions