Molecular development of the lateral geniculate nucleus in the absence of retinal waves during the time of retinal axon eye-specific segregation.
When retinal waves are inhibited binocularly, eye-specific segregation of retinal axons is disrupted, and retinal axons from the two eyes remain intermingled in the lateral geniculate nucleus (LGN). This effect of binocular retinal wave inhibition is mediated by the lack of activity-dependent competition between retinal axons from the two eyes, but it is unknown whether this effect is also mediated by the developmental arrest of the LGN in an immature state. Here we find developmental markers of the LGN during eye-specific segregation. The expression levels of Purkinje cell protein 4 (PCP4/PEP19), transcription factor 7-like 2 (TCF7L2/TCF4) and LIM homeobox protein 9 (Lhx9) in the LGN change significantly during eye-specific segregation. Using PCP4, TCF7L2 and Lhx9 as developmental markers of the LGN, we examine whether LGN development is affected by binocular disruption of retinal waves during eye-specific segregation. Binocular injection of epibatidine strongly inhibits eye-specific segregation, whereas it does not affect the expression of PCP4, TCF7L2 and Lhx9. Furthermore, the expression of PCP4, TCF7L2 and Lhx9 is normal in binocularly enucleated animals and in mice treated with the monoamine oxidase A (MAOA) inhibitor, clorgyline. In addition, our experiments using LGN slice cultures show that the expression of PCP4 and TCF7L2 in LGN slices changes as in vivo. Our results suggest that LGN development proceeds, at least in part, even in the absence of retinal inputs. PCP4, TCF7L2 and Lhx9 should be useful to examine LGN development during eye-specific segregation in mice and in ferrets.
Iwai
L
L
Department of Molecular and Systems Neurobiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kawasaki
H
H
D000818:Animals; D000831:Animals, Newborn; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage; D003010:Clorgyline / Q000008:administration & dosage; D015353:Eye Enucleation; D005289:Ferrets; D005829:Geniculate Bodies / Q000187:drug effects / Q000254:growth & development*; D018398:Homeodomain Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D060850:LIM-Homeodomain Proteins; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018722:Nicotinic Agonists / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D012160:Retina / Q000187:drug effects / Q000254:growth & development*; D055351:Retinal Neurons / Q000187:drug effects / Q000502:physiology*; D051820:TCF Transcription Factors / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D014795:Visual Pathways / Q000187:drug effects / Q000254:growth & development
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C497574:Lef1 protein, mouse; C117058:Lhx9 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; C489091:Pcp4 protein, mouse; D011725:Pyridines; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D003010:Clorgyline; C082748:epibatidine