A POU domain transcription factor-dependent program regulates axon pathfinding in the vertebrate visual system

Axon pathfinding relies on the ability of the growth cone to detect and int erpret guidance cues and to modulate cytoskeletal changes in response to th ese signals. We report that the murine POU domain transcription factor Brn- 3.2 regulates pathfinding in retinal ganglion cell (RGC) axons at multiple points along their pathways and the establishment of topographic order in t he superior colliculus. Using representational difference analysis, we iden tified Brn-3.2 gene targets likely to act on axon guidance at the levels of transcription, cell-cell interaction, and signal transduction, including t he actin-binding LIM domain protein abLIM. We present evidence that abLIM p lays a crucial role in RGC axon pathfinding, sharing functional similarity with its C. elegans homolog, UNC-115. Our findings provide insights into a Brn-3.2-directed hierarchical program linking signaling events to cytoskele tal changes required for axon pathfinding.