Chemokine signaling guides axons within the retina in zebrafish.
Chemokines are a large family of secreted proteins that play an important role in the migration of leukocytes during hematopoiesis and inflammation. Chemokines and their receptors are also widely distributed in the CNS. Although recent investigations are beginning to elucidate chemokine function within the CNS, relatively little is known about the CNS function of this important class of molecules. To better appreciate the CNS function of chemokines, the role of signaling by stromal cell-derived factor-1 (SDF-1) through its receptor, chemokine (CXC motif) receptor 4 (CXCR4), was analyzed in zebrafish embryos. The SDF-1/CXCR4 expression pattern suggested that SDF-1/CXCR4 signaling was important for guiding retinal ganglion cell axons within the retina to the optic stalk to exit the retina. Antisense knockdown of the ligand and/or receptor and a genetic CXCR4 mutation both induced retinal axons to follow aberrant pathways within the retina. Furthermore, retinal axons deviated from their normal pathway and extended to cells ectopically expressing SDF-1 within the retina. These data suggest that chemokine signaling is both necessary and sufficient for directing retinal growth cones within the retina.
Li
Qin
Q
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-1048, USA.
Shirabe
Komei
K
Thisse
Christine
C
Thisse
Bernard
B
Okamoto
Hitoshi
H
Masai
Ichiro
I
Kuwada
John Y
JY
D000818:Animals; D030801:Animals, Genetically Modified; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D020439:Growth Cones / Q000502:physiology* / Q000648:ultrastructure; D009030:Mosaicism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D009900:Optic Nerve / Q000166:cytology* / Q000196:embryology; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012160:Retina / Q000196:embryology / Q000648:ultrastructure*; D012165:Retinal Ganglion Cells / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D020319:Oligodeoxyribonucleotides, Antisense; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins
Curr Opin Neurobiol. 1999 Jun;9(3):355-63
10395576
Development. 2000 May;127(9):1953-60
10751183
Annu Rev Immunol. 2000;18:217-42
10837058
J Neurosci. 2000 Jul 1;20(13):4962-74
10864954
J Neurosci. 2000 Jul 1;20(13):4975-82
10864955
J Neurosci. 2000 Jul 1;20(13):4983-91
10864956
Nat Genet. 2000 Oct;26(2):216-20
11017081
Genome Res. 2000 Dec;10(12):1890-902
11116085
Dev Biol. 2001 Feb 1;230(1):1-17
11161558
Science. 2001 Apr 20;292(5516):507-10
11313496
Mech Dev. 2001 Dec;109(2):347-54
11731248
Neuron. 2002 Jan 17;33(2):205-17
11804569
Neuron. 2002 Jan 17;33(2):219-32
11804570
Nat Neurosci. 2002 Sep;5(9):843-8
12161754
Bioessays. 2002 Sep;24(9):821-7
12210518
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16297-302
12444253
Cell. 2002 Nov 27;111(5):647-59
12464177
J Neurovirol. 2002 Dec;8(6):573-84
12476351
Nature. 2003 Jan 16;421(6920):279-82
12508118
J Comp Neurol. 2003 Feb 24;457(1):1-6
12541320
J Neurosci. 2003 Feb 15;23(4):1360-71
12598624
Development. 2003 Jun;130(11):2479-94
12702661
Development. 2003 Jul;130(13):2967-80
12756179
J Neurosci. 2003 May 15;23(10):4190-8
12764107
J Neurosci. 2003 Jun 1;23(11):4601-12
12805300
Development. 1992 Dec;116(4):1021-32
1295726
Dev Dyn. 2003 Nov;228(3):358-69
14579375
Dev Biol. 2004 May 1;269(1):123-36
15081362
Nature. 1990 Dec 20-27;348(6303):728-30
2259382
Neuron. 1990 May;4(5):669-79
2344406
Dev Dyn. 1995 Jul;203(3):253-310
8589427
Mol Cell Neurosci. 1997;9(4):293-313
9268507
Neuron. 1997 Sep;19(3):575-89
9331350
Development. 1998 Aug;125(15):2983-93
9655820