Evidence map›Paper›PMID 25383527›Full record

ArticleNature2014

A relative shift in cloacal location repositions external genitalia in amniote evolution.

Patrick Tschopp, Emma Sherratt, Thomas J Sanger, Anna C Groner, Ariel C Aspiras, Jimmy K Hu, Olivier Pourquié, Jérôme Gros, Clifford J Tabin

Open access · greenAbstract read
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 91 citations in OpenAlex.

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  4. Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.Developmental dynamics : an official publication of the American Association of Anatomists · 2025
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  10. Assessing evolutionary and developmental transcriptome dynamics in homologous cell types.Developmental dynamics : an official publication of the American Association of Anatomists · 2022
    Article
  11. Article
  12. Theories, laws, and models in evo-devo.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2022
    Review
  13. Limb positioning and initiation: An evolutionary context of pattern and formation.Developmental dynamics : an official publication of the American Association of Anatomists · 2021
    Review
  14. Article
  15. Diversification of the vertebrate limb: sequencing the events.Current opinion in genetics & development · 2021
    Review
  16. Review
  17. Article
  18. Discrete Hedgehog Factor Expression and Action in the Developing Phallus.International journal of molecular sciences · 2020
    Article
  19. Article
  20. Article
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

9 authors at 3 institutions in 1 country.

Patrick TschoppDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Emma SherrattDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Thomas J SangerDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Anna C GronerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Ariel C AspirasDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jimmy K HuDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Olivier Pourquié1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 67400 Illkirch, France [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Jérôme GrosDevelopmental and Stem Cell Biology Department, Institut Pasteur, 75724 Paris Cedex 15, France.
Clifford J TabinDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Harvard University · USBrigham and Women's Hospital · USUniversity of Florida · US

Funding

Hedgehog Signaling and Organogenesis of the LimbR37HD032443 · NICHD · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI TABIN, CLIFFORD J. · 2005 to 2014
$5.3M
The reprogramming of limb progenitor cellsR01HD032443 · NICHD · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CLIFFORD J. TABIN · 1995 to 2026
$4.6M
NICHD NIH HHS R01 HD032443NICHD NIH HHS R37 HD032443NICHD NIH HHS R37-HD032443
6 · The paper itself

Abstract

The move of vertebrates to a terrestrial lifestyle required major adaptations in their locomotory apparatus and reproductive organs. While the fin-to-limb transition has received considerable attention, little is known about the developmental and evolutionary origins of external genitalia. Similarities in gene expression have been interpreted as a potential evolutionary link between the limb and genitals; however, no underlying developmental mechanism has been identified. We re-examined this question using micro-computed tomography, lineage tracing in three amniote clades, and RNA-sequencing-based transcriptional profiling. Here we show that the developmental origin of external genitalia has shifted through evolution, and in some taxa limbs and genitals share a common primordium. In squamates, the genitalia develop directly from the budding hindlimbs, or the remnants thereof, whereas in mice the genital tubercle originates from the ventral and tail bud mesenchyme. The recruitment of different cell populations for genital outgrowth follows a change in the relative position of the cloaca, the genitalia organizing centre. Ectopic grafting of the cloaca demonstrates the conserved ability of different mesenchymal cells to respond to these genitalia-inducing signals. Our results support a limb-like developmental origin of external genitalia as the ancestral condition. Moreover, they suggest that a change in the relative position of the cloacal signalling centre during evolution has led to an altered developmental route for external genitalia in mammals, while preserving parts of the ancestral limb molecular circuitry owing to a common evolutionary origin.

Indexed as

Biological EvolutionAnimalsCell LineageCloacaGene Expression ProfilingGene Expression Regulation, DevelopmentalGenitaliaMicePhylogenySignal TransductionSnakesTissue TransplantationX-Ray Microtomography

Identifiers

PMID25383527
PMCPMC4294627
OpenAlexW1965024447

What OpenQuestion holds

Textmetadata
LicenceTDM
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.