Evidence map›Paper›PMID 40121501›Full record

ArticleEvoDevo2025

Functional evidence supports the potential role of Tbx4-HLEA in the hindlimb degeneration of cetaceans.

Zhenhua Zhang, Yao Liu, Na Liang, Zhenpeng Yu, Luoying Deme, Duo Xu, Jia Liu, Wenhua Ren, Shixia Xu, Guang Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EvoDevo, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

10 authors.

Zhenhua ZhangJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Yao LiuJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Na LiangJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Zhenpeng YuJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Luoying DemeJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Duo XuJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Jia LiuJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Wenhua RenJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
Shixia XuJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China. xushixia78@163.com.
Guang YangJiangsu Key Laboratory for the Conservation and Utilization of Biodiversity in the Middle and Lower Reaches of the Yangtze River, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China. gyang@njnu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The evolution of limb morphology plays an important role in animal adaptation to different ecological niches. To fully adapt to aquatic life, cetaceans underwent hindlimb degeneration and forelimb transformed into flipper; however, the molecular mechanisms underlying the limb changes in cetaceans remain unclear. We previous study had shown that the Tbx4 hindlimb enhancer A (Tbx4-HLEA) in cetaceans exhibited specific deletions and nucleotide substitutions, with significantly reduced regulatory activity. To further investigate whether cetacean HLEA has a potential impact on hindlimb development in vivo, a knock-in mouse model was generated by knocking in the homologous cetacean HLEA in the present study. Phenotypic analysis showed a significant reduction in hindlimb bud development in homozygous knock-in mice at embryonic day (E)10.5; however, the phenotypic difference was rescued after E11.5. Transcriptomic and epigenetic analyses indicated that the cetacean HLEA acts as an enhancer in the mouse embryos and significantly reduces the transcriptional expression levels of Tbx4 at E10.5, supporting that downregulation of cetaceans HLEA regulatory activity reduces the expression of Tbx4. Additionally, both the number of activated non-coding elements and chromatin accessibility near Tbx4 were increased in homozygous knock-in mice at E11.5. The functional redundancy of enhancers compensated for the functional defect of cetacean HLEA, rescuing the expression level of Tbx4, and may account for the phenotype restoration after E11.5. In conclusion, our study suggested that the evolution of cetacean HLEA may be an important link with relevant molecular mechanism for the hindlimb degeneration.

Indexed as

CetaceansHindlimb degenerationKnock-in micePhenotypic rescueTbx4-HLEA

Identifiers

PMID40121501
PMCPMC11929173

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.