ArticleDevelopmental biology2020
Foxa1 and Foxa2 orchestrate development of the urethral tube and division of the embryonic cloaca through an autoregulatory loop with Shh.
Article in Developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- PPDPF is not a key regulator of human pancreas development.PLoS genetics · 2025Article
- gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling.Scientific reports · 2025Article
- 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
- FOXA1 in Breast Cancer: A Luminal Marker with Promising Prognostic and Predictive Impact.Cancers · 2022Article
- FOXA1 transcription activates TFF1 to reduce 6-OHDA-induced dopaminergic neuron damage.Experimental and therapeutic medicine · 2022Article
- Phenotype expansion of variants affecting p38 MAPK signaling in hypospadias patients.Orphanet journal of rare diseases · 2022Article
- Spatiotemporal map of key signaling factors during early penis development.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- COG6-CDG: Novel variants and novel malformation.Birth defects research · 2022Article
- Gene and protein expression profiles of olfactory ensheathing cells from olfactory bulbNeural regeneration research · 2022Article
- Single cell transcriptomic analysis of external genitalia reveals complex and sexually dimorphic cell populations in the early genital tubercle.Developmental biology · 2021Article
- Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Identification of Differentially Expressed Genes in Non-functioning Pituitary Adenoma by Transcriptome Analysis.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Congenital anomalies of external genitalia affect approximately 1 in 125 live male births. Development of the genital tubercle, the precursor of the penis and clitoris, is regulated by the urethral plate epithelium, an endodermal signaling center. Signaling activity of the urethral plate is mediated by Sonic hedgehog (SHH), which coordinates outgrowth and patterning of the genital tubercle by controlling cell cycle kinetics and expression of downstream genes. The mechanisms that govern Shh transcription in urethral plate cells are largely unknown. Here we show that deletion of Foxa1 and Foxa2 results in persistent cloaca, an incomplete separation of urinary, genital, and anorectal tracts, and severe hypospadias, a failure of urethral tubulogenesis. Loss of Foxa2 and only one copy of Foxa1 results in urethral fistula, an additional opening of the penile urethra. Foxa1/a2 participate in an autoregulatory feedback loop with Shh, in which FOXA1 and FOXA2 positively regulate transcription of Shh in the urethra, and SHH feeds back to negatively regulate Foxa1 and Foxa2 expression. These findings reveal novel roles for Foxa genes in development of the urethral tube and in division of the embryonic cloaca.
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Registered trials
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