ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Hypothalamic dysregulation and infertility in mice lacking the homeodomain protein Six6.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
50 citing papers in PubMed, 75 citations in OpenAlex.
- A single-nucleus multiomic study of preoptic area cells in prepubertal control vs prenatally androgenized female mice.Endocrinology · 2026Article
- Pan-tissue transcriptomic profiling of dairy cattle.Journal of animal science and biotechnology · 2026Article
- The Transcription Factors Six3 and Six6 in Neuromedin-S Neurons Differentially Affect Circadian Rhythms.Journal of neuroscience research · 2026Article
- A large-effect locus underlies migration timing in North American Atlantic salmon (Salmo salar).Scientific reports · 2026Article
- Brain-Specific Gata4 Downregulation in Greywick Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Transcriptomic profiling of murine GnRH neurons reveals developmental trajectories linked to human reproduction and infertility.Theranostics · 2025Article
- Lactate-Dependent Cross-Talk Between Astrocyte and GnRH-I Neurons in Hypothalamus of Aged Brain: Decreased GnRH-I Transcription.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Chemogenetic Depletion of Hypophysiotropic GnRH Neurons Does Not Affect Fertility in Mature Female Zebrafish.International journal of molecular sciences · 2022Article
- Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge.Endocrinology · 2022Review
- Article
- NovelMolecular vision · 2022Article
- Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter.Skeletal muscle · 2021Article
- The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice.Journal of neuroscience research · 2021Article
- Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells.Endocrinology · 2021Article
- A fish with no sex: gonadal and adrenal functions partition between zebrafish NR5A1 co-orthologs.Genetics · 2021Article
- The SIX Family of Transcription Factors: Common Themes Integrating Developmental and Cancer Biology.Frontiers in cell and developmental biology · 2021Review
- Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH, Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions.International journal of molecular sciences · 2020Review
- Steelhead (Evolutionary applications · 2020Article
- The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function.Molecular neurobiology · 2020Article
- Transcription Profiles of Age-at-Maturity-Associated Genes Suggest Cell Fate Commitment Regulation as a Key Factor in the Atlantic Salmon Maturation Process.G3 (Bethesda, Md.) · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The hypothalamus, pituitary, and gonads coordinate to direct the development and regulation of reproductive function in mammals. Control of the hypothalamic-pituitary-gonadal axis is dependent on correct migration of gonadotropin-releasing hormone (GnRH) neurons from the nasal placode to the hypothalamus, followed by proper synthesis and pulsatile secretion of GnRH, functions absent in patients with hypogonadal hypogonadism. In this study, we identify sine oculis-related homeobox 6 (Six6) as a novel factor necessary for proper targeting of GnRH expression to the limited population of GnRH neurons within the adult mouse hypothalamus and demonstrate that it is required for proper reproductive function in both male and female mice. Female Six6-null mice exhibit a striking decrease in fertility, failing to progress through the estrous cycle normally, show any signs of successful ovulation, or produce litters. Although basal gonadotropin production in these mice is relatively normal, analysis of GnRH expression reveals a dramatic decrease in total GnRH neuron numbers. We show that expression of Six6 is dramatically increased during GnRH neuronal maturation and that overexpression of Six6 induces GnRH transcription in neuronal cells. Finally, we demonstrate that this induction in GnRH expression is mediated via binding of Six6 to evolutionarily conserved ATTA sites located within the GnRH proximal promoter. Together, these data indicate that Six6 plays an important role in the regulation of GnRH expression and hypothalamic control of fertility.
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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.