A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors.
Despite increasing evidence for transcriptional control of neural connectivity, how transcription factors regulate discrete steps in axon guidance remains obscure. Projection neurons in the dorsal spinal cord relay sensory signals to higher brain centers. Some projection neurons send their axons ipsilaterally, whereas others, commissural neurons, send axons contralaterally. We show that two closely related LIM homeodomain proteins, Lhx2 and Lhx9, are expressed by a set of commissural relay neurons (dI1c neurons) and are required for the dI1c axon projection. Midline crossing by dI1c axons is lost in Lhx2/9 double mutants, a defect that results from loss of expression of Rig-1 from dI1c axons. Lhx2 binds to a conserved motif in the Rig-1 gene, suggesting that Lhx2/9 regulate directly the expression of Rig-1. Our findings reveal a link between the transcriptional programs that define neuronal subtype identity and the expression of receptors that guide distinctive aspects of their trajectory.
Wilson
Sara I
SI
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
Shafer
Beth
B
Lee
Kevin J
KJ
Dodd
Jane
J
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004622:Embryo, Mammalian; D007839:Functional Laterality / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000145:classification / Q000166:cytology / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C485867:Barhl2 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; C117058:Lhx9 protein, mouse; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases