Evidence map›Paper›PMID 29437009›Full record

ArticleCurrent molecular medicine2018

The bHLH Protein Nulp1 is Essential for Femur Development Via Acting as a Cofactor in Wnt Signaling in Drosophila.

Q Zeng, Y Wan, P Zhu, M Zhao, F Jiang, J Chen, M Tang, X Zhu, Y Li, H Zha and 13 more

Open access · bronzeAbstract read
In one paragraph

Article in Current molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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

23 authors at 6 institutions in 2 countries.

Q ZengThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Y WanThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
P ZhuCardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
M ZhaoDepartment of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha, 410013, China.
F JiangThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
J ChenCardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
M TangThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
X ZhuCardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
Y LiThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
H ZhaThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Y WangThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
M HuThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
X MoThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Y ZhangThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Y ChenThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Y ChenThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
X YeThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
R BodmerDevelopment, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, United States.
K OcorrDevelopment, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, United States.
Z JiangThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
J ZhuangCardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510100, China.
W YuanThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
X WuThe Center for Heart Development, State Key Laboratory of Development Biology, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China.
Hunan Normal University · CNGuangdong Academy of Medical Sciences · CNDiscovery Institute · USGuangdong General Hospital · CNSanford Burnham Prebys Medical Discovery Institute · USThird Xiangya Hospital · CN

Funding

Cellular/molecular substrates linking channel dysfunction and pathological cardiac remodelingR01HL132241 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI OCORR, KAREN · 2017 to 2020
$1.9M
NHLBI NIH HHS R01 HL132241
6 · The paper itself

Abstract

backgroundThe basic helix-loop-helix (bHLH) protein families are a large class of transcription factors, which are associated with cell proliferation, tissue differentiation, and other important development processes. We reported that the Nuclear localized protein-1 (Nulp1) might act as a novel bHLH transcriptional factor to mediate cellular functions. However, its role in development in vivo remains unknown.

methodsNulp1 (dNulp1) mutants are generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal. Expression of Wg target genes are analyzed by qRT-PCR. We use the Top-Flash luciferase reporter assay to response to Wg signaling.

resultsHere we show that Drosophila Nulp1 (dNulp1) mutants, generated by CRISPR/Cas9 targeting the Domain of Unknown Function (DUF654) in its C terminal, are partially homozygous lethal and the rare escapers have bent femurs, which are similar to the major manifestation of congenital bent-bone dysplasia in human Stuve- Weidemann syndrome. The fly phenotype can be rescued by dNulp1 over-expression, indicating that dNulp1 is essential for fly femur development and survival. Moreover, dNulp1 overexpression suppresses the notch wing phenotype caused by the overexpression of sgg/GSK3β, an inhibitor of the canonical Wnt cascade. Furthermore, qRT-PCR analyses show that seven target genes positively regulated by Wg signaling pathway are down-regulated in response to dNulp1 knockout, while two negatively regulated Wg targets are up-regulated in dNulp1 mutants. Finally, dNulp1 overexpression significantly activates the Top-Flash Wnt signaling reporter.

conclusionWe conclude that bHLH protein dNulp1 is essential for femur development and survival in Drosophila by acting as a positive cofactor in Wnt/Wingless signaling.

Indexed as

Wnt Signaling PathwayAmino Acid SequenceAnimalsAnimals, Genetically ModifiedBasic Helix-Loop-Helix ProteinsCell NucleusDrosophila melanogasterDrosophila ProteinsFemurGene Expression Regulation, DevelopmentalPhenotypePhylogenySequence HomologyTranscriptional ActivationWnt1 ProteinWnt ProteinsBasic Helix-Loop-Helix ProteinsDrosophila Proteinswg protein, DrosophilaWnt1 ProteinWnt ProteinsbHLHCRISPR/Cas9dNulp1Drosophila.femurWnt/Wg signaling

Identifiers

PMID29437009
PMCPMC5898038
OpenAlexW2792468169

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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.