Evidence map›Paper›PMID 18485195›Full record

ArticleBMC developmental biology2008

Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors.

François M Delporte, Vincent Pasque, Nathalie Devos, Isabelle Manfroid, Marianne L Voz, Patrick Motte, Frédéric Biemar, Joseph A Martial, Bernard Peers

Open access · hybridAbstract read
In one paragraph

Article in BMC developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 54 citations in OpenAlex.

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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

9 authors at 2 institutions in 3 countries.

François M DelporteUnit of Molecular Biology and Genetic Engineering, University of Liège, Giga-R, B34, Avenue de l'hôpital, 1, B-4000 Liège, Belgium. fdelporte@ulg.ac.be
Vincent Pasque
Nathalie Devos
Isabelle Manfroid
Marianne L Voz
Patrick Motte
Frédéric Biemar
Joseph A Martial
Bernard Peers
University of Liège · BETemple University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPAX6 is a transcription factor playing a crucial role in the development of the eye and in the differentiation of the pancreatic endocrine cells as well as of enteroendocrine cells. Studies on the mouse Pax6 gene have shown that sequences upstream from the P0 promoter are required for expression in the lens and the pancreas; but there remain discrepancies regarding the precise location of the pancreatic regulatory elements.

resultsDue to genome duplication in the evolution of ray-finned fishes, zebrafish has two pax6 genes, pax6a and pax6b. While both zebrafish pax6 genes are expressed in the developing eye and nervous system, only pax6b is expressed in the endocrine cells of the pancreas. To investigate the cause of this differential expression, we used a combination of in silico, in vivo and in vitro approaches. We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. Deletion analyses indicate that strong pancreatic expression of the pax6b gene relies on the combined action of two conserved regulatory enhancers, called regions A and C. By means of gel shift assays, we detected binding of the homeoproteins PDX1, PBX and PREP to several cis-elements of these regions. In constrast, regions A and C of the zebrafish pax6a gene are not active in the pancreas, this difference being attributable to sequence divergences within two cis-elements binding the pancreatic homeoprotein PDX1.

conclusionOur data indicate a conserved role of enhancers A and C in the pancreatic expression of pax6b and emphasize the importance of the homeoproteins PBX and PREP cooperating with PDX1, in activating pax6b expression in endocrine pancreatic cells. This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair.

Indexed as

Enhancer Elements, GeneticAnimalsAnimals, Genetically ModifiedBase SequenceConserved SequenceDNA-Binding ProteinsEye ProteinsGene Expression Regulation, DevelopmentalGreen Fluorescent ProteinsHomeodomain ProteinsMolecular Sequence DataMultiprotein ComplexesPaired Box Transcription FactorsPancreasPAX6 Transcription FactorPromoter Regions, GeneticDNA-Binding ProteinsEye ProteinsGreen Fluorescent ProteinsHomeodomain ProteinsMultiprotein ComplexesPaired Box Transcription Factorspancreatic and duodenal homeobox 1 proteinPax6 protein, mousePAX6 Transcription FactorRecombinant Fusion ProteinsRepressor ProteinsRNA, MessengerTrans-ActivatorsTranscription FactorsZebrafish Proteins

Identifiers

PMID18485195
PMCPMC2409314
OpenAlexW2044775986

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LicenceCC BY
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Registered trials

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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.