ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Disruption of ephrin signaling associates with disordered axophilic migration of the gonadotropin-releasing hormone neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- Transcriptomic profiling of murine GnRH neurons reveals developmental trajectories linked to human reproduction and infertility.Theranostics · 2025Article
- Chemogenetic Depletion of Hypophysiotropic GnRH Neurons Does Not Affect Fertility in Mature Female Zebrafish.International journal of molecular sciences · 2022Article
- Expression of p11 and Heteromeric TASK Channels in Rat Carotid Body Glomus Cells and Nerve Growth Factor-differentiated PC12 Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Article
- Harnessing the Power of Eph/ephrin Biosemiotics for Theranostic Applications.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Neurogenesis From Neural Crest Cells: Molecular Mechanisms in the Formation of Cranial Nerves and Ganglia.Frontiers in cell and developmental biology · 2020Review
- Nasal Placode Development, GnRH Neuronal Migration and Kallmann Syndrome.Frontiers in cell and developmental biology · 2019Article
- Novel Roles and Mechanism for Krüppel-like Factor 16 (KLF16) Regulation of Neurite Outgrowth and Ephrin Receptor A5 (EphA5) Expression in Retinal Ganglion Cells.The Journal of biological chemistry · 2016Article
- Transcriptional regulation of cranial sensory placode development.Current topics in developmental biology · 2015Review
- CXC chemokine receptor 7 (CXCR7) affects the migration of GnRH neurons by regulating CXCL12 availability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Suppression of β1-integrin in gonadotropin-releasing hormone cells disrupts migration and axonal extension resulting in severe reproductive alterations.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Dysregulation of Semaphorin7A/β1-integrin signaling leads to defective GnRH-1 cell migration, abnormal gonadal development and altered fertility.Human molecular genetics · 2011Article
- Reproductive dysfunction and decreased GnRH neurogenesis in a mouse model of CHARGE syndrome.Human molecular genetics · 2011Article
- Deletion of Otx2 in GnRH neurons results in a mouse model of hypogonadotropic hypogonadism.Molecular endocrinology (Baltimore, Md.) · 2011Article
- The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent.BMC genomics · 2011Article
- The gonadotropin-releasing hormone cell-specific element is required for normal puberty and estrous cyclicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Hypothalamic dysregulation and infertility in mice lacking the homeodomain protein Six6.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Gonadotropin-releasing hormone (GnRH) neuron migration: initiation, maintenance and cessation as critical steps to ensure normal reproductive function.Frontiers in neuroendocrinology · 2011Review
- From nose to brain: development of gonadotrophin-releasing hormone-1 neurones.Journal of neuroendocrinology · 2010Review
- Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling.Nature · 2009Article
- New tricks by an old dogma: mechanisms of the Organizational/Activational Hypothesis of steroid-mediated sexual differentiation of brain and behavior.Hormones and behavior · 2009Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Ephrin signaling is involved in repulsive and attractive interactions mediating axon guidance and cell-boundary formation in the developing nervous system. As a result of a fortuitous transgene integration event, we have identified here a potential role for EphA5 in the axophilic migration of gonadotropin-releasing hormone (GnRH) neurons from the nasal placode into the brain along ephrin-expressing vomeronasal axons. Transgene integration in the GNR23 mouse line resulted in a 26 kb deletion in chromosome 5, approximately 67 kb 3' to Epha5. This induced a profound, region-specific upregulation of EphA5 mRNA and protein expression in the developing mouse brain. The GnRH neurons in GNR23 mice overexpressed EphA5 from embryonic day 11, whereas ephrin A3 and A5 mRNA levels in olfactory neurons were unchanged. The GnRH neurons were found to be slow in commencing their migration from the olfactory placode and also to form abnormal clusters of cells on the olfactory axons, prohibiting their migration out of the nose. As a result, adult hemizygous mice had only 40% of the normal complement of GnRH neurons in the brain, whereas homozygous mice had <15%. This resulted in infertility in adult female homozygous GNR23 mice, suggesting that some cases of human hypogonadotropic hypogonadism may result from ephrin-related mutations. These data provide evidence for a role of EphA-ephrin signaling in the axophilic migration of the GnRH neurons during embryogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.