Reference : The Pax6b homeodomain is dispensable for pancreatic endocrine cell differentiation in...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/100889
The Pax6b homeodomain is dispensable for pancreatic endocrine cell differentiation in zebrafish.
English
Verbruggen, Vincianne [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Ek, Olivier [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Georlette, Daphne [Temple University, Philadelphia, Pennsylvania > Department of Biology > > >]
Delporte, Francois [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Von Berg, Virginie mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Detry, Nathalie mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Biemar, Frederic [Temple University, Philadelphia, Pennsylvania > Department of Biology > > >]
Coutinho, Pedro [Western General Hospital > > Medical Research Council Human Genetics Unit > >]
Martial, Joseph mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Voz, Marianne mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Manfroid, Isabelle mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Peers, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
30-Apr-2010
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
285
18
13863-73
Yes (verified by ORBi)
International
0021-9258
1083-351X
Baltimore
MD
[en] Animals ; Cell Differentiation/physiology ; Endocrine Cells/cytology/metabolism ; Eye Proteins/genetics/metabolism ; Glucagon/biosynthesis/genetics ; Homeodomain Proteins/genetics/metabolism ; Mutation ; Paired Box Transcription Factors/genetics/metabolism ; Pancreas/cytology/embryology ; RNA Splicing/physiology ; Repressor Proteins/genetics/metabolism ; Zebrafish/embryology/genetics ; Zebrafish Proteins/genetics/metabolism
[en] Pax6 is a well conserved transcription factor that contains two DNA-binding domains, a paired domain and a homeodomain, and plays a key role in the development of eye, brain, and pancreas in vertebrates. The recent identification of the zebrafish sunrise mutant, harboring a mutation in the pax6b homeobox and presenting eye abnormalities but no obvious pancreatic defects, raised a question about the role of pax6b in zebrafish pancreas. We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. Through the use of various morpholinos targeting intron-exon junctions, pax6b RNA splicing was perturbed at several sites, leading either to retention of intronic sequences or to deletion of exonic sequences in the pax6b transcript. By this strategy, we show that deletion of the Pax6b homeodomain in zebrafish embryos does not disturb pancreas development, whereas lens formation is strongly affected. These data thus provide the explanation for the lack of pancreatic defects in the sunrise pax6b mutants. In addition, partial reduction of Pax6b function in zebrafish embryos performed by injection of small amounts of pax6b morpholinos caused a clear rise in alpha cell number and in glucagon expression, emphasizing the importance of the fine tuning of the Pax6b level to its biological activity.
Giga-Development and Stem Cells
http://hdl.handle.net/2268/100889
10.1074/jbc.M110.108019
http://www.jbc.org/content/285/18/13863.long#aff-2

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