Stromal Cell-Derived Factor-1 (Chemokine C-X-C Motif Ligand 12) and Chemokine C-X-C Motif Receptor 4 Are Required for Migration of Gonadotropin-Releasing Hormone Neurons to the Forebrain

Abstract

Gonadotropin-releasing hormone (GnRH) neurons migrate from the vomeronasal organ (VNO) in the nasal compartment to the basal forebrain in mice, beginning on embryonic day 11 (E11). These neurons use vomeronasal axons as guides to migrate through the nasal mesenchyme. Most GnRH neurons then migrate along the caudal branch of the vomeronasal nerve to reach the hypothalamus. We show here that stromal cell-derived factor-1 [SDF-1, also known as chemokine C-X-C motif ligand 12 (CXCL12)] is expressed in the embryonic nasal mesenchyme from as early as E10 in an increasing rostral to caudal gradient that is most intense at the border of the nasal mesenchyme and the telencephalon. Chemokine C-X-C motif receptor 4 (CXCR4), the receptor for SDF-1, is expressed by neurons in the olfactory epithelium and VNO. Cells derived from these sensory epithelia, including migrating GnRH neurons and ensheathing glial precursors of the migrating mass (MM), also express CXCR4, suggesting that they may use SDF-1 as a chemokine. In support of this, most GnRH neurons of CXCR4 Ϫ/Ϫ mice fail to exit the VNO at E13, and comparatively few GnRH neurons reach the forebrain. There is also a significant decrease in the total number of GnRH neurons in CXCR4 Ϫ/Ϫ mice and an increase in cell death within the VNO relative to controls. The MM is smaller in CXCR4 Ϫ/Ϫ mice, suggesting that some MM cells also require SDF-1/CXCR4 function for migration and survival.

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

“…Thus, the temporal-and region-specific aspects of receptor variability, as impacted by either genetic or epigenetic factors, may have dissociable effects on psychiatric disease risk at different points of the life course, adding a layer of complexity to our understanding of psychiatric risk alleles. This is consistent with findings in multiple systems where a particular molecule has a different role during development compared with adulthood (Laurent et al, 2002;Schwarting et al, 2006;Young-Davies et al, 2000). For example, serotonin transporter blockers such as fluoxetine appear to have opposite effects during development, where they increase anxiety, than in adulthood, where they decrease anxiety (Ansorge et al, 2004).…”

Roles of Chemokine Receptor 4 (CXCR4) and Chemokine Ligand 12 (CXCL12) in Metastasis of Hepatocellular Carcinoma Cells

“…Many studies suggest that tumor cell migration and organspecific metastasis are critically regulated by chemokines and their receptors (21)(22)(23)(24)(25)(26)(27)(28)(29). The axis of CXCR4/CXCL12 plays an important role in metastasis of many tumors (9)(10)(11)(12)(13)(14)(22)(23)(24)(25).…”

“…The axis of CXCR4/CXCL12 plays an important role in metastasis of many tumors (9)(10)(11)(12)(13)(14)(22)(23)(24)(25). Abnormal expression of CXCR4 or CXCL12 has been observed in solid tumors such as ovarian cancer (30), rhabdomysarcoma (26), nasopharyngeal carcinoma (21), melanoma (27), colorectal cancer (28), pancreatic cancer (24), and breast cancer (7).…”

Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology

“…Similarly, Knaut et al (2005) reported that trigeminal sensory ganglia (TgSG) neurons were ectopically located in the CXC4b morphant zebrafish embryos (embryos injected with morpholine-conjugated antisense oligonucleotides) while both the number of TgSG neurons and axon projections were normal. In CXCR4−/− mice, most GnRH neurons also failed to exit the vomeronasal organ (VNO) at E13, and comparatively few GnRH neurons reached the forebrain (Schwarting GA et al, 2006). Primordial germ cells (PGCs) are the founders of sperm or oocytes.…”