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

Linda Erkman, Paul A. Yates, Todd McLaughlin, Robert J. McEvilly, Thomas Whisenhunt, Shawn M. O'Connell, Anna I. Krones, Michael A. Kirby, David H. Rapaport, John R. Bermingham, Dennis D.M. O'Leary, Michael G. Rosenfeld

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Axon pathfinding relies on the ability of the growth cone to detect and interpret guidance cues and to modulate cytoskeletal changes in response to these 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 the superior colliculus. Using representational difference analysis, we identified Brn-3.2 gene targets likely to act on axon guidance at the levels of transcription, cell-cell interaction, and signal transduction, including the actin-binding LIM domain protein abLIM. We present evidence that abLIM plays 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 cytoskeletal changes required for axon pathfinding.

Original languageEnglish
Pages (from-to)779-792
Number of pages14
JournalNeuron
Volume28
Issue number3
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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