The immune protein CD3zeta is required for normal development of neural circuits in the retina.
Emerging evidence suggests that immune proteins regulate activity-dependent synapse formation in the central nervous system (CNS). Mice with mutations in class I major histocompatibility complex (MHCI) genes have incomplete eye-specific segregation of retinal ganglion cell (RGC) axon projections to the CNS. This effect has been attributed to causes that are nonretinal in origin. We show that a key component of MHCI receptor, CD3zeta, is expressed in RGCs. CD3zeta-deficient mice have reduced RGC dendritic motility, an increase in RGC dendritic density, and a selective defect of glutamate-receptor-mediated synaptic activity in the retina. Disrupted RGC synaptic activity and dendritic motility is associated with a failure of eye-specific segregation of RGC axon projections to the CNS. These results provide direct evidence of an unrecognized requirement for immune proteins in the developmental regulation of RGC synaptic wiring and indicate a possible retinal origin for the disruption of eye-specific segregation found in immune-deficient mice.
Xu
Hong-ping
HP
Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Chen
Hui
H
Ding
Qian
Q
Xie
Zheng-Hua
ZH
Chen
Ling
L
Diao
Ling
L
Wang
Ping
P
Gan
Lin
L
Crair
Michael C
MC
Tian
Ning
N
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism*; D002465:Cell Movement; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000254:growth & development* / Q000378:metabolism; D017470:Receptors, Glutamate / Q000502:physiology; D012160:Retina / Q000254:growth & development* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development / Q000378:metabolism
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D017470:Receptors, Glutamate; D018698:Glutamic Acid