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CXCR4/SDF‐1 system modulates development of GnRH‐1 neurons and the olfactory system
Author(s) -
Toba Yoko,
Tiong Jean D.,
Ma Qing,
Wray Susan
Publication year - 2008
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20594
Subject(s) - biology , vomeronasal organ , olfactory ensheathing glia , olfactory epithelium , olfactory bulb , olfactory system , forebrain , axon , neuroscience , microbiology and biotechnology , medicine , endocrinology , central nervous system
Abstract 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. © 2008 Wiley Periodicals, Inc. Develop Neurobiol 2008