Evidence map›Paper›PMID 24632946›Full record

ArticleCell death and differentiation2014

Disruption of the temporally regulated cloaca endodermal β-catenin signaling causes anorectal malformations.

S Miyagawa, M Harada, D Matsumaru, K Tanaka, C Inoue, C Nakahara, R Haraguchi, S Matsushita, K Suzuki, N Nakagata and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.5field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  10. The role of p63 in embryonic external genitalia outgrowth in mice.Development, growth & differentiation · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

S Miyagawa1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan [3] Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Aichi, Japan.
M Harada1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan [3] Unit of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
D Matsumaru1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
K Tanaka1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
C Inoue1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
C Nakahara1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
R Haraguchi1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan [3] Department of Molecular Pathology, Ehime University Graduate School of Medicine, Ehime, Japan.
S MatsushitaDepartment of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
K Suzuki1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
N NakagataDivision of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
R C-L NgDepartment of Surgery, The University of Hong Kong, Hong Kong SAR, China.
K AkitaUnit of Clinical Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
V C-H LuiDepartment of Surgery, The University of Hong Kong, Hong Kong SAR, China.
G Yamada1] Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan [2] Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Wakayama Medical University · JPKumamoto University · JPUniversity of Hong Kong · HKTokyo Medical and Dental University · JP

Funding

EXTERNAL GENITALIA DEVELOPMENT AND HYPOSPADIASR01ES016597 · NIEHS · WASHINGTON UNIVERSITY · PI MA, LIANG · 2009 to 2013
$1.5M
NIEHS NIH HHS R01 ES016597NIEHS NIH HHS R01ES016597
6 · The paper itself

Abstract

The cloaca is temporally formed and eventually divided by the urorectal septum (URS) during urogenital and anorectal organ development. Although congenital malformations, such as anorectal malformations (ARMs), are frequently observed during this process, the underlying pathogenic mechanisms remain unclear. β-Catenin is a critical component of canonical Wnt signaling and is essential for the regulation of cell differentiation and morphogenesis during embryogenesis. The expression of β-catenin is observed in endodermal epithelia, including URS epithelia. We modulated the β-catenin gene conditionally in endodermal epithelia by utilizing tamoxifen-inducible Cre driver line (Shh(CreERT2)). Both β-catenin loss- and gain-of-function (LOF and GOF) mutants displayed abnormal clefts in the perineal region and hypoplastic elongation of the URS. The mutants also displayed reduced cell proliferation in the URS mesenchyme. In addition, the β-catenin GOF mutants displayed reduced apoptosis and subsequently increased apoptosis in the URS epithelium. This instability possibly resulted in reduced expression levels of differentiation markers, such as keratin 1 and filaggrin, in the perineal epithelia. The expression of bone morphogenetic protein (Bmp) genes, such as Bmp4 and Bmp7, was also ectopically induced in the epithelia of the URS in the β-catenin GOF mutants. The expression of the Msx2 gene and phosphorylated-Smad1/5/8, possible readouts of Bmp signaling, was also increased in the mutants. Moreover, we introduced an additional mutation for a Bmp receptor gene: BmprIA. The Shh(CreERT2/+); β-catenin(flox(ex3)/+); BmprIA(flox/-) mutants displayed partial restoration of URS elongation compared with the β-catenin GOF mutants. These results indicate that some ARM phenotypes in the β-catenin GOF mutants were caused by abnormal Bmp signaling. The current analysis revealed the close relation of endodermal β-catenin signaling to the ARM phenotypes. These results are considered to shed light on the pathogenic mechanisms of human ARMs.

Indexed as

AnimalsAnorectal MalformationsAnus, Imperforatebeta CateninCloacaEndodermFilaggrin ProteinsGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansMiceWnt Signaling Pathwaybeta CateninFilaggrin ProteinsFLG protein, humanHomeodomain ProteinsMSX2 protein

Identifiers

PMID24632946
PMCPMC4013517
OpenAlexW2073909863

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.