Stromal cell-derived factor-1 antagonizes slit/robo signaling in vivo.
Retinal ganglion cell axons exit the eye, enter the optic stalk, cross the ventral midline at the optic chiasm, and terminate in the optic tectum of the zebrafish. While in the optic stalk, they grow immediately adjacent to cells expressing the powerful retinal axon repellent slit2. The chemokine stromal cell-derived factor-1 (SDF1) is expressed within the optic stalk and its receptor CXCR4 is expressed in retinal ganglion cells. SDF1 makes cultured retinal axons less responsive to slit2. Here, we show that reducing SDF1 signaling in vivo rescues retinal axon pathfinding errors in zebrafish mutants that have a partial functional loss of the slit receptor robo2. In contrast, reducing SDF1 signaling in animals that completely lack the robo2 receptor does not rescue retinal guidance errors. These results demonstrate that endogenous levels of SDF1 antagonize the repellent effects of slit/robo signaling in vivo and that this antagonism is important during axonal pathfinding.
Chalasani
Sreekanth H
SH
Neuroscience Department, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Sabol
Angela
A
Xu
Hong
H
Gyda
Michael A
MA
Rasband
Kendall
K
Granato
Michael
M
Chien
Chi-Bin
CB
Raper
Jonathan A
JA
D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000097905:Roundabout Proteins
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D047908:Intracellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4; D011971:Receptors, Immunologic; D029961:Zebrafish Proteins; C504432:Slit2 protein, zebrafish; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins