Reference : Nkx6.1 and nkx6.2 regulate alpha- and beta-cell formation in zebrafish by acting on panc...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/72125
Nkx6.1 and nkx6.2 regulate alpha- and beta-cell formation in zebrafish by acting on pancreatic endocrine progenitor cells.
English
Binot, Anne-Catherine [> >]
Manfroid, Isabelle mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Flasse, Lydie [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
Winandy, Marie mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-Management : Plate-forme zebrafish > >]
Motte, Patrick mailto [Université de Liège - ULg > Département des sciences de la vie > Génomique fonctionnelle et imagerie moléculaire végétale > >]
Martial, Joseph 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 > >]
Voz, Marianne mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire > >]
1-Feb-2010
Developmental Biology
Academic Press
340
2
397-407
Yes (verified by ORBi)
International
0012-1606
1095-564X
Orlando
FL
[en] Animals ; Embryo, Nonmammalian/cytology/embryology/metabolism ; Homeodomain Proteins/genetics/metabolism ; In Situ Hybridization ; Islets of Langerhans/cytology/physiology ; Microinjections ; Oligonucleotides, Antisense/pharmacology ; Stem Cells/cytology ; Transcription Factors/genetics/metabolism ; Zebrafish/embryology/genetics/metabolism ; Zebrafish Proteins/genetics/metabolism
[en] In mice, the Nkx6 genes are crucial to alpha- and beta-cell differentiation, but the molecular mechanisms by which they regulate pancreatic subtype specification remain elusive. Here it is shown that in zebrafish, nkx6.1 and nkx6.2 are co-expressed at early stages in the first pancreatic endocrine progenitors, but that their expression domains gradually segregate into different layers, nkx6.1 being expressed ventrally with respect to the forming islet while nkx6.2 is expressed mainly in beta-cells. Knockdown of nkx6.2 or nkx6.1 expression leads to nearly complete loss of alpha-cells but has no effect on beta-, delta-, or epsilon-cells. In contrast, nkx6.1/nkx6.2 double knockdown leads additionally to a drastic reduction of beta-cells. Synergy between the effects of nkx6.1 and nkx6.2 knockdown on both beta- and alpha-cell differentiation suggests that nkx6.1 and nkx6.2 have the same biological activity, the required total nkx6 threshold being higher for alpha-cell than for beta-cell differentiation. Finally, we demonstrate that the nkx6 act on the establishment of the pancreatic endocrine progenitor pool whose size is correlated with the total nkx6 expression level. On the basis of our data, we propose a model in which nkx6.1 and nkx6.2, by allowing the establishment of the endocrine progenitor pool, control alpha- and beta-cell differentiation.
Giga-Development and Stem Cells
http://hdl.handle.net/2268/72125
10.1016/j.ydbio.2010.01.025
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WDG-4Y95V53-3&_user=532038&_coverDate=04%2F15%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000026659&_version=1&_urlVersion=0&_userid=532038&md5=3a3863671ac9d4816cb0cb318b4db213&searchtype=a
Copyright (c) 2010 Elsevier Inc. All rights reserved.

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