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

[en] Background NEUROG3 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. Results We show herein 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 a couple of bHLH 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. Conclusions This 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.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Flasse, Lydie ; Université de Liège - ULiège > Stem Cells-Zebrafish Dev. & Disease Model

Pirson, Justine ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Stern, David ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Von Berg, Virginie ; Université de Liège - ULiège > GIGA-Research

Manfroid, Isabelle ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Peers, Bernard ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Voz, Marianne ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire

Language :

English

Title :

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

Publication date :

July 2013

Journal title :

BMC Biology

eISSN :

1741-7007

Publisher :

BioMed Central

Volume :

Pages :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 08 July 2013

Statistics

Number of views

150 (26 by ULiège)

Number of downloads

283 (8 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Desgraz R, Bonal C, Herrera PL. β-cell regeneration: the pancreatic intrinsic faculty. Trends Endocrinol Metab 2011, 22:34-43. 10.1016/j.tem.2010.09.004, 21067943.
Prince VE, Kinkel MD. Recent advances in pancreas development: from embryonic pathways to programming renewable sources of beta cells. F1000 Biol Rep 2010, 2:17. 2863342,2863342, 20445833.
Tuduri E, Kieffer TJ. Reprogramming gut and pancreas endocrine cells to treat diabetes. Diabetes Obes Metab 2011, 13:53-59.
Zaret KS, Grompe M. Generation and regeneration of cells of the liver and pancreas. Science 2008, 322:1490-1494. 10.1126/science.1161431, 2641009, 19056973.
Stafford D, Hornbruch A, Mueller PR, Prince VE. A conserved role for retinoid signaling in vertebrate pancreas development. Dev Genes Evol 2004, 214:432-441.
D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006, 24:1392-1401. 10.1038/nbt1259, 17053790.
Chung WS, Andersson O, Row R, Kimelman D, Stainier DY. Suppression of Alk8-mediated Bmp signaling cell-autonomously induces pancreatic beta-cells in zebrafish. Proc Natl Acad Sci U S A 2010, 107:1142-1147. 10.1073/pnas.0910205107, 2824271, 20080554.
Chung WS, Shin CH, Stainier DY. Bmp2 signaling regulates the hepatic versus pancreatic fate decision. Dev Cell 2008, 15:738-748. 10.1016/j.devcel.2008.08.019, 2610857, 19000838.
Chung WS, Stainier DY. Intra-endodermal interactions are required for pancreatic beta cell induction. Dev Cell 2008, 14:582-593. 10.1016/j.devcel.2008.02.012, 2396532, 18410733.
Manfroid I, Delporte F, Baudhuin A, Motte P, Neumann CJ, Voz ML, Martial JA, Peers B. Reciprocal endoderm-mesoderm interactions mediated by fgf24 and fgf10 govern pancreas development. Development 2007, 134:4011-4021. 10.1242/dev.007823, 17942484.
Naye F, Voz ML, Detry N, Hammerschmidt M, Peers B, Manfroid I. Essential roles of zebrafish bmp2a, fgf10, and fgf24 in the specification of the ventral pancreas. Mol Biol Cell 2012, 23:945-954. 10.1091/mbc.E11-08-0664, 3290651, 22219376.
Stafford D, Prince VE. Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development. Curr Biol 2002, 12:1215-1220. 10.1016/S0960-9822(02)00929-6, 12176331.
Ober EA, Field HA, Stainier DY. From endoderm formation to liver and pancreas development in zebrafish. Mech Dev 2003, 120:5-18. 10.1016/S0925-4773(02)00327-1, 12490292.
Biemar F, Argenton F, Schmidtke R, Epperlein S, Peers B, Driever W. Pancreas development in zebrafish: early dispersed appearance of endocrine hormone expressing cells and their convergence to form the definitive islet. Dev Biol 2001, 230:189-203. 10.1006/dbio.2000.0103, 11161572.
Field HA, Dong PD, Beis D, Stainier DY. Formation of the digestive system in zebrafish. II. Pancreas morphogenesis. Dev Biol 2003, 261:197-208. 10.1016/S0012-1606(03)00308-7, 12941629.
Hesselson D, Anderson RM, Beinat M, Stainier DY. Distinct populations of quiescent and proliferative pancreatic beta-cells identified by HOTcre mediated labeling. Proc Natl Acad Sci U S A 2009, 106:14896-14901. 10.1073/pnas.0906348106, 2736433, 19706417.
Wang Y, Rovira M, Yusuff S, Parsons MJ. Genetic inducible fate mapping in larval zebrafish reveals origins of adult insulin-producing beta-cells. Development 2011, 138:609-617. 10.1242/dev.059097, 3026409, 21208992.
Esni F, Ghosh B, Biankin AV, Lin JW, Albert MA, Yu X, MacDonald RJ, Civin CI, Real FX, Pack MA, Ball DW, Leach SD. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Development 2004, 131:4213-4224. 10.1242/dev.01280, 15280211.
Yee NS, Lorent K, Pack M. Exocrine pancreas development in zebrafish. Dev Biol 2005, 284:84-101. 10.1016/j.ydbio.2005.04.035, 15963491.
Zecchin E, Filippi A, Biemar F, Tiso N, Pauls S, Ellertsdottir E, Gnugge L, Bortolussi M, Driever W, Argenton F. Distinct delta and jagged genes control sequential segregation of pancreatic cell types from precursor pools in zebrafish. Dev Biol 2007, 301:192-204. 10.1016/j.ydbio.2006.09.041, 17059815.
Kim W, Shin YK, Kim BJ, Egan JM. Notch signaling in pancreatic endocrine cell and diabetes. Biochem Biophys Res Commun 2010, 392:247-251. 10.1016/j.bbrc.2009.12.115, 20035712.
Bertrand N, Castro DS, Guillemot F. Proneural genes and the specification of neural cell types. Nat Rev Neurosci 2002, 3:517-530. 10.1038/nrn874, 12094208.
Rukstalis JM, Habener JF. Neurogenin3: a master regulator of pancreatic islet differentiation and regeneration. Islets 2009, 1:177-184. 10.4161/isl.1.3.9877, 21099270.
Apelqvist A, Li H, Sommer L, Beatus P, Anderson DJ, Honjo T, Hrabe de Angelis M, Lendahl U, Edlund H. Notch signalling controls pancreatic cell differentiation. Nature 1999, 400:877-881. 10.1038/23716, 10476967.
Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci U S A 2000, 97:1607-1611. 10.1073/pnas.97.4.1607, 26482, 10677506.
Grapin-Botton A, Majithia AR, Melton DA. Key events of pancreas formation are triggered in gut endoderm by ectopic expression of pancreatic regulatory genes. Genes Dev 2001, 15:444-454. 10.1101/gad.846001, 312631, 11230152.
Gasa R, Mrejen C, Lynn FC, Skewes-Cox P, Sanchez L, Yang KY, Lin CH, Gomis R, German MS. Induction of pancreatic islet cell differentiation by the neurogenin-neuroD cascade. Differentiation 2008, 76:381-391. 10.1111/j.1432-0436.2007.00228.x, 17924961.
Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD, German MS. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 2000, 127:3533-3542.
Naya FJ, Huang HP, Qiu Y, Mutoh H, DeMayo FJ, Leiter AB, Tsai MJ. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes Dev 1997, 11:2323-2334. 10.1101/gad.11.18.2323, 316513, 9308961.
Wang X, Chu LT, He J, Emelyanov A, Korzh V, Gong Z. A novel zebrafish bHLH gene, neurogenin3, is expressed in the hypothalamus. Gene 2001, 275:47-55. 10.1016/S0378-1119(01)00648-5, 11574151.
Fiuza UM, Arias AM. Cell and molecular biology of Notch. J Endocrinol 2007, 194:459-474. 10.1677/JOE-07-0242, 17761886.
Fior R, Henrique D. " Notch-Off" : a perspective on the termination of Notch signalling. Int J Dev Biol 2009, 53:1379-1384. 10.1387/ijdb.072309rf, 19247952.
Ehebauer M, Hayward P, Arias AM. Notch, a universal arbiter of cell fate decisions. Science 2006, 314:1414-1415. 10.1126/science.1134042, 17138893.
Zebrafish Mutant Resource http://www.sanger.ac.uk/Projects/D_rerio/zmp/.
Wang Y, Chen K, Yao Q, Zheng X, Yang Z. Phylogenetic analysis of zebrafish basic helix-loop-helix transcription factors. J Mol Evol 2009, 68:629-640. 10.1007/s00239-009-9232-7, 19449054.
Dalgin G, Ward AB, Hao le T, Beattie CE, Nechiporuk A, Prince VE. Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas. Development 2011, 138:4597-4608. 10.1242/dev.067736, 3190380, 21989909.
Mavropoulos A, Devos N, Biemar F, Zecchin E, Argenton F, Edlund H, Motte P, Martial JA, Peers B. sox4b is a key player of pancreatic alpha cell differentiation in zebrafish. Dev Biol 2005, 285:211-223. 10.1016/j.ydbio.2005.06.024, 16055112.
Soyer J, Flasse L, Raffelsberger W, Beucher A, Orvain C, Peers B, Ravassard P, Vermot J, Voz ML, Mellitzer G, Gradwohl G. Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. Development 2010, 137:203-212. 10.1242/dev.041673, 2799156, 20040487.
Itoh M, Kim CH, Palardy G, Oda T, Jiang YJ, Maust D, Yeo SY, Lorick K, Wright GJ, Ariza-McNaughton L, Weissman AM, Lewis J, Chandrasekharappa SC, Chitnis AB. Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 2003, 4:67-82. 10.1016/S1534-5807(02)00409-4, 12530964.
Obholzer N, Wolfson S, Trapani JG, Mo W, Nechiporuk A, Busch-Nentwich E, Seiler C, Sidi S, Sollner C, Duncan RN, Boehland A, Nicolson T. Vesicular glutamate transporter 3 is required for synaptic transmission in zebrafish hair cells. J Neurosci 2008, 28:2110-2118. 10.1523/JNEUROSCI.5230-07.2008, 18305245.
Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 2003, 17:2591-2603. 10.1101/gad.269003, 218152, 14561778.
Wendik B, Maier E, Meyer D. Zebrafish mnx genes in endocrine and exocrine pancreas formation. Dev Biol 2004, 268:372-383. 10.1016/j.ydbio.2003.12.026, 15063174.
Delporte FM, Pasque V, Devos N, Manfroid I, Voz ML, Motte P, Biemar F, Martial JA, Peers B. Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors. BMC Dev Biol 2008, 8:53. 10.1186/1471-213X-8-53, 2409314, 18485195.
Nikolaou N, Watanabe-Asaka T, Gerety S, Distel M, Koster RW, Wilkinson DG. Lunatic fringe promotes the lateral inhibition of neurogenesis. Development 2009, 136:2523-2533. 10.1242/dev.034736, 2709061, 19553285.
Amoyel M, Cheng YC, Jiang YJ, Wilkinson DG. Wnt1 regulates neurogenesis and mediates lateral inhibition of boundary cell specification in the zebrafish hindbrain. Development 2005, 132:775-785. 10.1242/dev.01616, 15659486.
Pogoda HM, von der Hardt S, Herzog W, Kramer C, Schwarz H, Hammerschmidt M. The proneural gene ascl1a is required for endocrine differentiation and cell survival in the zebrafish adenohypophysis. Development 2006, 133:1079-1089. 10.1242/dev.02296, 16481349.
Parsons MJ, Pisharath H, Yusuff S, Moore JC, Siekmann AF, Lawson N, Leach SD. Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech Dev 2009, 126:898-912. 10.1016/j.mod.2009.07.002, 3640481, 19595765.
Ninov N, Borius M, Stainier DY. Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors. Development 2012, 139:1557-1567. 10.1242/dev.076000, 3317964, 22492351.
Manfroid I, Ghaye A, Naye F, Detry N, Palm S, Pan L, Ma TP, Huang W, Rovira M, Martial JA, Parsons MJ, Moens CB, Voz ML, Peers B. Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration. Dev Biol 2012, 366:268-278. 10.1016/j.ydbio.2012.04.002, 3364407, 22537488.
Binot AC, Manfroid I, Flasse L, Winandy M, Motte P, Martial JA, Peers B, Voz ML. Nkx6.1 and nkx6.2 regulate alpha- and beta-cell formation in zebrafish by acting on pancreatic endocrine progenitor cells. Dev Biol 2010, 340:397-407. 10.1016/j.ydbio.2010.01.025, 20122912.
Wilson ME, Scheel D, German MS. Gene expression cascades in pancreatic development. Mech Dev 2003, 120:65-80. 10.1016/S0925-4773(02)00333-7, 12490297.
Jensen J. Gene regulatory factors in pancreatic development. Dev Dyn 2004, 229:176-200. 10.1002/dvdy.10460, 14699589.
Cau E, Casarosa S, Guillemot F. Mash1 and Ngn1 control distinct steps of determination and differentiation in the olfactory sensory neuron lineage. Development 2002, 129:1871-1880.
Chien CT, Hsiao CD, Jan LY, Jan YN. Neuronal type information encoded in the basic-helix-loop-helix domain of proneural genes. Proc Natl Acad Sci U S A 1996, 93:13239-13244. 10.1073/pnas.93.23.13239, 24077, 8917575.
Jarman AP, Grau Y, Jan LY, Jan YN. atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell 1993, 73:1307-1321. 10.1016/0092-8674(93)90358-W, 8324823.
Powell LM, Zur Lage PI, Prentice DR, Senthinathan B, Jarman AP. The proneural proteins Atonal and Scute regulate neural target genes through different E-box binding sites. Mol Cell Biol 2004, 24:9517-9526. 10.1128/MCB.24.21.9517-9526.2004, 522279, 15485919.
Logan MA, Steele MR, Van Raay TJ, Vetter ML. Identification of shared transcriptional targets for the proneural bHLH factors Xath5 and XNeuroD. Dev Biol 2005, 285:570-583. 10.1016/j.ydbio.2005.06.033, 16112102.
Gerber AN, Klesert TR, Bergstrom DA, Tapscott SJ. Two domains of MyoD mediate transcriptional activation of genes in repressive chromatin: a mechanism for lineage determination in myogenesis. Genes Dev 1997, 11:436-450. 10.1101/gad.11.4.436, 9042858.
Quan XJ, Denayer T, Yan J, Jafar-Nejad H, Philippi A, Lichtarge O, Vleminckx K, Hassan BA. Evolution of neural precursor selection: functional divergence of proneural proteins. Development 2004, 131:1679-1689. 10.1242/dev.01055, 15084454.
Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S, Sealy I, Caccamo M, Churcher C, Scott C, Barrett JC, Koch R, Rauch GJ, White S, Chow W, Kilian B, Quintais LT, Guerra-Assunção JA, Zhou Y, Gu Y, Yen J, Vogel JH, Eyre T, Redmond S, Banerjee R, et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature 2013, 496:498-503. 10.1038/nature12111, 23594743.
Wang S, Hecksher-Sorensen J, Xu Y, Zhao A, Dor Y, Rosenberg L, Serup P, Gu G. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Dev Biol 2008, 317:531-540. 10.1016/j.ydbio.2008.02.052, 2423199, 18394599.
Kokubu H, Ohtsuka T, Kageyama R. Mash1 is required for neuroendocrine cell development in the glandular stomach. Genes Cells 2008, 13:41-51.
Jenny M, Uhl C, Roche C, Duluc I, Guillermin V, Guillemot F, Jensen J, Kedinger M, Gradwohl G. Neurogenin3 is differentially required for endocrine cell fate specification in the intestinal and gastric epithelium. EMBO J 2002, 21:6338-6347. 10.1093/emboj/cdf649, 136953, 12456641.
Lee CS, Perreault N, Brestelli JE, Kaestner KH. Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Genes Dev 2002, 16:1488-1497. 10.1101/gad.985002, 186338, 12080087.
Westerfield M. The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Danio rerio) 1995, Eugene, OR: M. Westerfield, 3.
Haddon C, Jiang YJ, Smithers L, Lewis J. Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant. Development 1998, 125:4637-4644.
Ensembl Genome Browser. http://www.ensembl.org/Danio_rerio/.
BLAST: Basic Local Alignment Search Tool http://blast.ncbi.nlm.nih.gov/Blast.cgi.
Allende ML, Weinberg ES. The expression pattern of two zebrafish achaete-scute homolog (ash) genes is altered in the embryonic brain of the cyclops mutant. Dev Biol 1994, 166:509-530. 10.1006/dbio.1994.1334, 7813774.
Korzh V, Edlund T, Thor S. Zebrafish primary neurons initiate expression of the LIM homeodomain protein Isl-1 at the end of gastrulation. Development 1993, 118:417-425.
Korzh V, Sleptsova I, Liao J, He J, Gong Z. Expression of zebrafish bHLH genes ngn1 and nrd defines distinct stages of neural differentiation. Dev Dyn 1998, 213:92-104. 10.1002/(SICI)1097-0177(199809)213:1<92::AID-AJA9>3.0.CO;2-T, 9733104.
Krauss S, Johansen T, Korzh V, Moens U, Ericson JU, Fjose A. Zebrafish pax[zf-a]: a paired box-containing gene expressed in the neural tube. EMBO J 1991, 10:3609-3619. 453092, 1718739.
Millimaki BB, Sweet EM, Dhason MS, Riley BB. Zebrafish atoh1 genes: classic proneural activity in the inner ear and regulation by Fgf and Notch. Development 2007, 134:295-305. 10.1242/dev.02734, 17166920.
Liao J, He J, Yan T, Korzh V, Gong Z. A class of neuroD-related basic helix-loop-helix transcription factors expressed in developing central nervous system in zebrafish. DNA Cell Biol 1999, 18:333-344. 10.1089/104454999315394, 10235116.
Kani S, Bae YK, Shimizu T, Tanabe K, Satou C, Parsons MJ, Scott E, Higashijima S, Hibi M. Proneural gene-linked neurogenesis in zebrafish cerebellum. Dev Biol 2010, 343:1-17. 10.1016/j.ydbio.2010.03.024, 20388506.
Masai I, Stemple DL, Okamoto H, Wilson SW. Midline signals regulate retinal neurogenesis in zebrafish. Neuron 2000, 27:251-263. 10.1016/S0896-6273(00)00034-9, 10985346.
Yao J, Zhou J, Liu Q, Lu D, Wang L, Qiao X, Jia W. Atoh8, a bHLH transcription factor, is required for the development of retina and skeletal muscle in zebrafish. PLoS One 2010, 5:e10945. 10.1371/journal.pone.0010945, 2880597, 20532172.
Miura H, Yanazawa M, Kato K, Kitamura K. Expression of a novel aristaless related homeobox gene 'Arx' in the vertebrate telencephalon, diencephalon and floor plate. Mech Dev 1997, 65:99-109. 10.1016/S0925-4773(97)00062-2, 9256348.
Milewski WM, Duguay SJ, Chan SJ, Steiner DF. Conservation of PDX-1 structure, function, and expression in zebrafish. Endocrinology 1998, 139:1440-1449. 10.1210/en.139.3.1440, 9492081.
Argenton F, Zecchin E, Bortolussi M. Early appearance of pancreatic hormone-expressing cells in the zebrafish embryo. Mech Dev 1999, 87:217-221. 10.1016/S0925-4773(99)00151-3, 10495291.
Pauls S, Zecchin E, Tiso N, Bortolussi M, Argenton F. Function and regulation of zebrafish nkx2.2a during development of pancreatic islet and ducts. Dev Biol 2007, 304:875-890. 10.1016/j.ydbio.2007.01.024, 17335795.
Robu ME, Larson JD, Nasevicius A, Beiraghi S, Brenner C, Farber SA, Ekker SC. p53 activation by knockdown technologies. PLoS Genet 2007, 3:e78. 10.1371/journal.pgen.0030078, 1877875, 17530925.