Evidence map›Paper›PMID 39562571›Full record

ArticleNature communications2024

A Huluwa phosphorylation switch regulates embryonic axis induction.

Yao Li, Yun Yan, Bo Gong, Qianwen Zheng, Haiyan Zhou, Jiarui Sun, Mingpeng Li, Zhao Wang, Yaohui Li, Yunjing Wan and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

16 authors.

Yao Li *Department of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yun Yan *Department of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Bo Gong *Department of Cell and Developmental Biology, Weill Cornell Medicine, Cornell University, 1300 York Avenue, New York, NY, 10065, USA.ORCID 0009-0009-8833-8084
Qianwen ZhengDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Haiyan ZhouDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Jiarui SunDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Mingpeng LiDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Zhao WangDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yaohui LiDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yunjing WanDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Weixi ChenDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Shiqian QiDepartment of Urology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.ORCID 0000-0002-7589-8877
Xianming MoDepartment of Pediatric Surgery and Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China.ORCID 0000-0003-3897-3126
Anming MengLaboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.ORCID 0000-0001-7228-3431
Bo XiangDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Jing ChenDepartment of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China. jingchen@scu.edu.cn.ORCID 0000-0001-5540-0878

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Embryonic axis formation is essential for patterning and morphogenesis in vertebrates and is tightly regulated by the dorsal organizer. Previously, we demonstrated that maternally derived Huluwa (Hwa) acts as a dorsal determinant, dictating axis formation by activating β-catenin signaling in zebrafish and Xenopus. However, the mechanism of activation and fine regulation of the Hwa protein remains unclear. Through candidate screening we identified a mutation at Ser168 in the PPNSP motif of Hwa that dramatically abolishes its axis-inducing activity. Mechanistically, mutating the Ser168 residue reduced its binding affinity to Tankyrase 1/2 and the degradation of the Axin protein, weakening β-catenin signaling activation. We confirmed that Ser168 is phosphorylated and that phosphorylation increases Hwa activity in β-catenin signaling and axis induction. Several kinases including Cdk16, Cdk2, and GSK3β, were found to enhance Ser168 phosphorylation in vitro and in vivo. Both dominant-negative Cdk16 expression and pHwa (Ser168) antibody treatment reduce Hwa function. Lastly, a knock-in allele mutating Ser168 to alanine resulted in embryos lacking body axes, demonstrating that Ser168 is essential to axis formation. In summary, Ser168 acts as a phosphorylation switch in Hwa/β-catenin signaling for embryonic axis induction, regulated by multiple kinases.

Indexed as

beta CateninZebrafishZebrafish ProteinsAnimalsAxin ProteinBody PatterningCyclin-Dependent KinasesEmbryo, NonmammalianGene Expression Regulation, DevelopmentalMutationPhosphorylationSignal TransductionTankyrasesXenopus ProteinsAxin Proteinbeta CateninCyclin-Dependent KinasesTankyrasesXenopus ProteinsZebrafish Proteins

Identifiers

PMID39562571
PMCPMC11576741

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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.