Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish

BMC Biology

Research Article

Virginie Von Berg¹  Marianne L Voz¹  Lydie C Flasse¹  Bernard Peers¹  David G Stern¹  Isabelle Manfroid¹  Justine L Pirson¹ 

[1] Laboratory of zebrafish development and disease models, University of Liege (ULg), 1, Giga-R, Avenue de l’Hopital, 1, 4000, Liege, Belgium;

关键词: Pancreas;    Endocrine;    Zebrafish;    Ascl1b;    Neurod1;    Neurog3;   

DOI  :  10.1186/1741-7007-11-78

 received in 2013-04-25, accepted in 2013-06-28,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundNEUROG3 is a key regulator of pancreatic endocrine cell differentiation in mouse, essential for the generation of all mature hormone producing cells. It is repressed by Notch signaling that prevents pancreatic cell differentiation by maintaining precursors in an undifferentiated state.ResultsWe show that, in zebrafish, neurog3 is not expressed in the pancreas and null neurog3 mutant embryos do not display any apparent endocrine defects. The control of endocrine cell fate is instead fulfilled by two basic helix-loop-helix factors, Ascl1b and Neurod1, that are both repressed by Notch signaling. ascl1b is transiently expressed in the mid-trunk endoderm just after gastrulation and is required for the generation of the first pancreatic endocrine precursor cells. Neurod1 is expressed afterwards in the pancreatic anlagen and pursues the endocrine cell differentiation program initiated by Ascl1b. Their complementary role in endocrine differentiation of the dorsal bud is demonstrated by the loss of all hormone-secreting cells following their simultaneous inactivation. This defect is due to a blockage of the initiation of endocrine cell differentiation.ConclusionsThis study demonstrates that NEUROG3 is not the unique pancreatic endocrine cell fate determinant in vertebrates. A general survey of endocrine cell fate determinants in the whole digestive system among vertebrates indicates that they all belong to the ARP/ASCL family but not necessarily to the Neurog3 subfamily. The identity of the ARP/ASCL factor involved depends not only on the organ but also on the species. One could, therefore, consider differentiating stem cells into insulin-producing cells without the involvement of NEUROG3 but via another ARP/ASCL factor.

【 授权许可】

Unknown   
© Flasse et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.