ArticleDevelopmental biology2014
Dkk1 in the peri-cloaca mesenchyme regulates formation of anorectal and genitourinary tracts.
Article in Developmental biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- ARM in ARM? Investigating the co-occurrence of anorectal malformations and labioscrotal anomalies.Pediatric surgery international · 2026Pooled it
- The cloacal outgrowth orchestrates co-development of the bladder and umbilical arteries.Development (Cambridge, England) · 2026Article
- Differentiation of human pluripotent stem cells into urothelial organoids via transient activation of WNT signaling.iScience · 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
- Anorectal malformations.Nature reviews. Disease primers · 2024Review
- Spatiotemporal map of key signaling factors during early penis development.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Pathogenesis of Anorectal Malformations in Retinoic Acid Receptor Knockout Mice Studied by HREM.Biomedicines · 2021Article
- Hedgehog Signaling for Urogenital Organogenesis and Prostate Cancer: An Implication for the Epithelial-Mesenchyme Interaction (EMI).International journal of molecular sciences · 2019Review
- Integrating lncRNAs and mRNAs expression profiles in terminal hindgut of fetal rats with anorectal malformations.Pediatric surgery international · 2018Article
- 16p11.2 transcription factorProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration.Development (Cambridge, England) · 2017Article
- Clarification of mammalian cloacal morphogenesis using high-resolution episcopic microscopy.Developmental biology · 2016Article
- Systematic stereoscopic analyses for cloacal development: The origin of anorectal malformations.Scientific reports · 2015Article
- Anorectal malformation: the etiological factors.Pediatric surgery international · 2015Review
- An illustrated anatomical ontology of the developing mouse lower urogenital tract.Development (Cambridge, England) · 2015Article
- Sequencing of the DKK1 gene in patients with anorectal malformations and hypospadias.European journal of pediatrics · 2015Article
- A mouse model of urofacial syndrome with dysfunctional urination.Human molecular genetics · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Anorectal malformation (ARM) is a common birth defect but the developmental history and the underlying molecular mechanism are poorly understood. Using murine genetic models, we report here that a signaling molecule Dickkopf-1 (Dkk1) is a critical regulator. The anorectal and genitourinary tracts are major derivatives of caudal hindgut, or the cloaca.Dkk1 is highly expressed in the dorsal peri-cloacal mesenchymal (dPCM) progenitors. We show that the deletion of Dkk1 causes the imperforate anus with rectourinary fistula. Mutant genital tubercles exhibit a preputial hypospadias phenotype and premature urethral canalization.Dkk1 mutants have an ectopic expansion of the dPCM tissue, which correlates with an aberrant increase of cell proliferation and survival. This ectopic tissue is detectable before the earliest sign of the anus formation, suggesting that it is most likely the primary or early cause of the defect. Deletion of Dkk1 results in an elevation of the Wnt/ß-catenin activity. Signaling molecules Shh, Fgf8 and Bmp4 are also upregulated. Furthermore, genetic hyperactivation of Wnt/ß-catenin signal pathway in the cloacal mesenchyme partially recapitulates Dkk1 mutant phenotypes. Together, these findings underscore the importance ofDKK1 in regulating behavior of dPCM progenitors, and suggest that formation of anus and urethral depends on Dkk1-mediated dynamic inhibition of the canonical Wnt/ß-catenin signal pathway.
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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.