Transcriptional networks controlling pancreatic development and beta cell function

被引:179
作者
Servitja, JM [1 ]
Ferrer, J [1 ]
机构
[1] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Spain
关键词
chromatin immunoprecipitation; gene networks; Haplo-insufficiency; Hnf1; alpha; Hnf beta; Hnf4; islets of Langerhans; MODY1; MODY3; Ngn3; Nkx2.2; Pdx1; Stem cells; Type 1 diabetes mellitus; Type 2 diabetes mellitus;
D O I
10.1007/s00125-004-1368-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Transcription factors provide the genetic instructions that drive pancreatic development and enable mature beta cells to function properly. To understand fully how this is accomplished, it is necessary to unravel the regulatory networks formed by transcription factors acting on their genomic targets. This article discusses recent advances in our understanding of how transcriptional networks control early pancreas organogenesis, embryonic endocrine cell formation and the differentiated function of adult beta cells. We discuss how mutations in several transcription factor genes involved in such networks cause Maturity onset diabetes of the young (MODY). Finally, we propose that pancreatic gene programs might be manipulated to generate beta cells or to enhance the function of existing beta cells, thereby providing a possible treatment of different forms of diabetes.
引用
收藏
页码:597 / 613
页数:17
相关论文
共 169 条
  • [1] Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells
    Ahlgren, U
    Pfaff, SL
    Jessell, TM
    Edlund, T
    Edlund, H
    [J]. NATURE, 1997, 385 (6613) : 257 - 260
  • [2] β-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes
    Ahlgren, U
    Jonsson, J
    Jonsson, L
    Simu, K
    Edlund, H
    [J]. GENES & DEVELOPMENT, 1998, 12 (12) : 1763 - 1768
  • [3] Error and attack tolerance of complex networks
    Albert, R
    Jeong, H
    Barabási, AL
    [J]. NATURE, 2000, 406 (6794) : 378 - 382
  • [4] Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development
    Annicotte, JS
    Fayard, E
    Swift, GH
    Selander, L
    Edlund, H
    Tanaka, T
    Kodama, T
    Schoonjans, K
    Auwerx, J
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (19) : 6713 - 6724
  • [5] Notch signalling controls pancreatic cell differentiation
    Apelqvist, Å
    Li, H
    Sommer, L
    Beatus, P
    Anderson, DJ
    Honjo, T
    de Angelis, MH
    Lendahl, U
    Edlund, H
    [J]. NATURE, 1999, 400 (6747) : 877 - 881
  • [6] Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas
    Apelqvist, A
    Ahlgren, U
    Edlund, H
    [J]. CURRENT BIOLOGY, 1997, 7 (10) : 801 - 804
  • [7] Barbacci E, 1999, DEVELOPMENT, V126, P4795
  • [8] A pancreatic β-cell-specific enhancer in the human PIX-1 gene is regulated by hepatocyte nuclear factor 3β (HNF-3β), HNF-1α, and SPs transcription factors
    Ben-Shushan, E
    Marshak, S
    Shoshkes, M
    Cerasi, E
    Melloul, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) : 17533 - 17540
  • [9] Noise in eukaryotic gene expression
    Blake, WJ
    Kærn, M
    Cantor, CR
    Collins, JJ
    [J]. NATURE, 2003, 422 (6932) : 633 - 637
  • [10] A transcription factor regulatory circuit in differentiated pancreatic cells
    Boj, SF
    Párrizas, M
    Maestro, MA
    Ferrer, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (25) : 14481 - 14486