ArticlePLoS genetics2020
GLI3 resides at the intersection of hedgehog and androgen action to promote male sex differentiation.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- The genetic landscape of hypospadias: clinical insights into inherited and de novo risk factors.Science China. Life sciences · 2026Article
- Desert Hedgehog mediates stem Leydig cell differentiation through Ptch2/Gli1/Sf1 signaling axis.eLife · 2026Article
- Social and Anxiety-Like Behaviors Are Affected in Juvenile Mice With Gli2Brain and behavior · 2026Article
- Prenatal Low Testosterone Levels Induced byBiomedicines · 2025Article
- Germline-Somatic Liaison Dictates Cancer Subtypes via de novo Steroid Biosynthesis.Cancer discovery · 2025Article
- Article
- High-resolution optical genome mapping unveils gene disruptions in a reciprocal chromosomal translocation and severe male infertility: a case report.Journal of assisted reproduction and genetics · 2025Article
- Single-cell resolution uncovers neighboring cell subtypes that share steroidogenic capacity during fetal testis development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Hedgehog Signaling Functions in Spermatogenesis and Keeping Hemolymph-Testis Barrier Stability inInternational journal of molecular sciences · 2025Article
- Oligogenic analysis across broad phenotypes of 46,XY differences in sex development associated with NR5A1/SF-1 variants: findings from the international SF1next study.EBioMedicine · 2025Article
- The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.Asian journal of andrology · 2024Article
- Fetal Leydig cells: What we know and what we don't.Molecular reproduction and development · 2024Review
- Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Potential benefit of rapid genetic testing for Pallister-Hall syndrome.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2023Article
- Genome-wide association study reveals genomic loci of sex differentiation and gonadal development inFrontiers in genetics · 2023Article
- Development of an in-vitro high-throughput screening system to identify modulators of genitalia development.PNAS nexus · 2023Article
- Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway.Communications biology · 2022Article
- Distinctive functioning of STARD1 in the fetal Leydig cells compared to adult Leydig and adrenal cells. Impact of Hedgehog signaling via the primary cilium.Molecular and cellular endocrinology · 2021Article
- Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling.Endocrinology · 2021Review
- Hedgehog signal disruption, gonadal dysgenesis and reproductive disorders: Is there a link to endocrine disrupting chemicals?Current research in toxicology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Urogenital tract abnormalities are among the most common congenital defects in humans. Male urogenital development requires Hedgehog-GLI signaling and testicular hormones, but how these pathways interact is unclear. We found that Gli3XtJ mutant mice exhibit cryptorchidism and hypospadias due to local effects of GLI3 loss and systemic effects of testicular hormone deficiency. Fetal Leydig cells, the sole source of these hormones in developing testis, were reduced in numbers in Gli3XtJ testes, and their functional identity diminished over time. Androgen supplementation partially rescued testicular descent but not hypospadias in Gli3XtJ mutants, decoupling local effects of GLI3 loss from systemic effects of androgen insufficiency. Reintroduction of GLI3 activator (GLI3A) into Gli3XtJ testes restored expression of Hedgehog pathway and steroidogenic genes. Together, our results show a novel function for the activated form of GLI3 that translates Hedgehog signals to reinforce fetal Leydig cell identity and stimulate timely INSL3 and testosterone synthesis in the developing testis. In turn, exquisite timing and concentrations of testosterone are required to work alongside local GLI3 activity to control development of a functionally integrated male urogenital tract.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.