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 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.
Erkman
L
L
Howard Hughes Medical Institute and, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Yates
P A
PA
McLaughlin
T
T
McEvilly
R J
RJ
Whisenhunt
T
T
O'Connell
S M
SM
Krones
A I
AI
Kirby
M A
MA
Rapaport
D H
DH
Bermingham
J R
JR
O'Leary
D D
DD
Rosenfeld
M G
MG
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002450:Cell Communication / Q000235:genetics; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D020439:Growth Cones / Q000378:metabolism; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009900:Optic Nerve / Q000473:pathology; D009901:Optic Nerve Diseases / Q000235:genetics / Q000473:pathology; D017434:Protein Structure, Tertiary; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D013477:Superior Colliculi / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014795:Visual Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
C107440:ABLIM1 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; C085559:Pou4f2 protein, mouse; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors