ArticleHuman molecular genetics2011
Dysregulation of Semaphorin7A/β1-integrin signaling leads to defective GnRH-1 cell migration, abnormal gonadal development and altered fertility.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 91 citations in OpenAlex.
- De novo rare EMX2 variants lead to idiopathic hypogonadotropic hypogonadism.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Secretory Profile Analysis of Human Granulosa Cell Line Following Gonadotropin Stimulation.International journal of molecular sciences · 2025Article
- Linking Adult Olfactory Neurogenesis to Social Reproductive Stimuli: Mechanisms and Functions.International journal of molecular sciences · 2024Review
- Case report: Novel SIN3A loss-of-function variant as causative for hypogonadotropic hypogonadism in Witteveen-Kolk syndrome.Frontiers in genetics · 2024Article
- A comprehensive review on lncRNA LOXL1-AS1: molecular mechanistic pathways of lncRNA LOXL1-AS1 in tumorigenicity of cancer cells.Frontiers in oncology · 2024Review
- Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B.International journal of ophthalmology · 2024Article
- SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability.Nature communications · 2023Article
- GnRH replacement rescues cognition in Down syndrome.Science (New York, N.Y.) · 2022Article
- Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis.Life (Basel, Switzerland) · 2022Article
- Comparative Transcriptomics Reveals the Key lncRNA and mRNA of Sunite Sheep Adrenal Gland Affecting Seasonal Reproduction.Frontiers in veterinary science · 2022Article
- Article
- The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency.International journal of molecular sciences · 2021Review
- Sex Steroids and the Shaping of the Peripubertal Brain: The Sexual-Dimorphic Set-Up of Adult Neurogenesis.International journal of molecular sciences · 2021Review
- Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease.Human genetics · 2021Review
- Kallmann syndrome and idiopathic hypogonadotropic hypogonadism: The role of semaphorin signaling on GnRH neurons.Handbook of clinical neurology · 2021Review
- Neuropilin-1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction.The EMBO journal · 2020Article
- Macphatics and PoEMs in Postpartum Mammary Development and Tumor Progression.Journal of mammary gland biology and neoplasia · 2020Review
- Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism.American journal of human genetics · 2020Article
- Article
- GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling.Frontiers in cellular neuroscience · 2019Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Reproduction in mammals is dependent on the function of specific neurons that secrete gonadotropin-releasing hormone-1 (GnRH-1). These neurons originate prenatally in the nasal placode and migrate into the forebrain along the olfactory-vomeronasal nerves. Alterations in this migratory process lead to defective GnRH-1 secretion, resulting in heterogeneous genetic disorders such as idiopathic hypogonadotropic hypogonadism (IHH), and other reproductive diseases characterized by the reduction or failure of sexual competence. Combining mouse genetics with in vitro models, we demonstrate that Semaphorin 7A (Sema7A) is essential for the development of the GnRH-1 neuronal system. Loss of Sema7A signaling alters the migration of GnRH-1 neurons, resulting in significantly reduced numbers of these neurons in the adult brain as well as in reduced gonadal size and subfertility. We also show that GnRH-1 cells differentially express the Sema7 receptors β1-integrin and Plexin C1 as a function of their migratory stage, whereas the ligand is robustly expressed along developing olfactory/vomeronasal fibers. Disruption of Sema7A function in vitro inhibits β1-integrin-mediated migration. Analysis of Plexin C1(-/-) mice did not reveal any difference in the migratory process of GnRH-1 neurons, indicating that Sema7A mainly signals through β1-integrin to regulate GnRH-1 cell motility. In conclusion, we have identified Sema7A as a gene implicated in the normal development of the GnRH-1 system in mice and as a genetic marker for the elucidation of some forms of GnRH-1 deficiency in humans.
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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.