The reelin pathway modulates the structure and function of retinal synaptic circuitry.
The formation of synaptic connections requires the coordination of specific guidance molecules and spontaneous neuronal activity. The visual system has provided a useful model for understanding the role of these cues in shaping the precise connections from the neural retina to the brain. Here, we demonstrate that two essential genes in the Reelin signaling pathway function during the patterning of synaptic connectivity in the retina. Physiological studies of mice deficient in either reelin or disabled-1 reveal an attenuation of rod-driven retinal responses. This defect is associated with a decrease in rod bipolar cell density and an abnormal distribution of processes in the inner plexiform layer. These results imply that, in addition to its essential role during neuronal migration, the Reelin pathway contributes to the formation of neuronal circuits in the central nervous system.
Rice
D S
DS
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Nusinowitz
S
S
Azimi
A M
AM
Martínez
A
A
Soriano
E
E
Curran
T
T
D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D002465:Cell Movement; D004596:Electroretinography; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism; D026502:LDL-Receptor Related Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D011973:Receptors, LDL / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000502:physiology; D000091042:Reelin Protein; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012697:Serine Endopeptidases; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D014795:Visual Pathways / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; C115785:DAB1 protein, human; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases