CXCR4/SDF-1 system modulates development of GnRH-1 neurons and the olfactory system.
Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 influence neuronal migration and have been identified in nasal regions. Gonadotropin releasing hormone-1 (GnRH-1) neurons migrate from nasal regions into the developing forebrain, where postnatally they control reproduction. This study examined the role of SDF-1/CXCR4 in development of the GnRH-1/olfactory systems. Migrating GnRH-1 neurons were CXCR4 immunopositive as were the fibers along which they migrate. SDF-1 transcripts were detected in olfactory epithelium and vomeronasal organ, while SDF-1 immunoreactivity highlighted the GnRH-1 migratory pathway. CXCR4-deficient mice showed a decrease in GnRH-1 cells at the nasal forebrain junction and in brain, but the overall migratory pathway remained intact, no ectopic GnRH-1 cells were detected and olfactory axons reached the olfactory bulb. To further characterize the influence of SDF-1/CXCR4 in the GnRH-1 system, nasal explants were used. CXCR4 expression in vitro was similar to that in vivo. SDF-1 was detected in a dorsal midline cell cluster as well as in migrating GnRH-1 cells. Treatment of explants with bicyclam AMD3100, a CXCR4 antagonist, attenuated GnRH-1 neuronal migration and sensory axon outgrowth. Moreover, the number of GnRH-1 neurons in the explant periphery was reduced. The effects were blocked by coincubation with SDF-1. Removal of midline SDF-1 cells did not alter directional outgrowth of olfactory axons. These results indicate that SDF-1/CXCR4 signaling in not necessary for olfactory axon guidance but rather influences sensory axon extension and GnRH-1 neuronal migration, and maintains GnRH-1 neuronal expression as the cells move away from nasal pit regions.
Toba
Yoko
Y
Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tiong
Jean D
JD
Ma
Qing
Q
Wray
Susan
S
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004622:Embryo, Mammalian; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D007834:Lasers; D051379:Mice; D042282:Microdissection; D009830:Olfactory Bulb / Q000196:embryology / Q000648:ultrastructure; D009831:Olfactory Mucosa / Q000378:metabolism / Q000648:ultrastructure; D009833:Olfactory Pathways / Q000196:embryology* / Q000648:ultrastructure; D018034:Olfactory Receptor Neurons / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D011498:Protein Precursors / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019147:Vomeronasal Organ / Q000378:metabolism / Q000648:ultrastructure
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D011498:Protein Precursors; D019718:Receptors, CXCR4; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone