Leukemia inhibitory factor inhibits neuronal development and disrupts synaptic organization in the mouse retina.
Leukemia inhibitory factor (LIF) belongs to the interleukin-6 cytokine family, all members of which signal through the common gp130 receptor. Neurotrophic members of this cytokine family are known to arrest photoreceptor maturation and are likely to regulate maturation of other retinal neurons as well. We have used transgenic mice that constitutively express LIF beginning in embryonic development to determine its effects on synaptic organization and molecular maturation of all classes of retinal neurons. LIF reduced the numbers of cells showing markers characteristic of mature cells of all neuronal classes and caused synaptic ectopia. The net effect was disrupted morphological development and disturbed synaptic organization. Our study suggests that cytokines signaling through gp130 are capable of regulating many aspects of neuronal differentiation in the retina, including synaptic targeting.
Sherry
David M
DM
University of Houston College of Optometry, Houston, Texas, USA.
Mitchell
Robert
R
Li
Haiyun
H
Graham
Dianca R
DR
Ash
John D
JD
D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D058966:Contactins; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics*; D053605:Leukemia Inhibitory Factor; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics
D015415:Biomarkers; D058966:Contactins; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules