Pancreas development is promoted by cyclopamine, a Hedgehog signaling inhibitor

被引:208
作者
Kim, SK
Melton, DA
机构
[1] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA
[2] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
关键词
D O I
10.1073/pnas.95.22.13036
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Exposure to cyclopamine, a steroid alkaloid that blocks Sonic hedgehog (Shh) signaling, promotes pancreatic expansion in embryonic chicks. Heterotopic development of pancreatic endocrine and exocrine structures occurs in regions adjacent to the pancreas including stomach and duodenum, and insulin-producing islets in the pancreas are enlarged. The homeodomain transcription factor PDX1, required for pancreas development, is expressed broadly in the posterior foregut but pancreas development normally initiates only in a restricted region of PDX1-expressing posterior foregut where endodermal Shh expression is repressed. The results suggests that cyclopamine expands the endodermal region where Shh signaling does not occur, resulting in pancreatic differentiation in a larger region of PDX1-expressing foregut endoderm, Cyclopamine reveals the capacity of a broad region of the posterior embryonic foregut to form pancreatic cells and provides a means for expanding embryonic pancreas development.
引用
收藏
页码:13036 / 13041
页数:6
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共 43 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] 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
  • [3] BARBOSA JJD, 1946, SURG GYNECOL OBSTET, V82, P527
  • [4] IMMUNOCYTOLOGIC STUDY OF DIFFERENTIATION OF ENDOCRINE PANCREAS IN CHICK-EMBRYO .2. GLUCAGON
    BEAUPAIN, D
    DIETERLE.F
    [J]. GENERAL AND COMPARATIVE ENDOCRINOLOGY, 1974, 23 (04) : 421 - 431
  • [5] Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly
    Belloni, E
    Muenke, M
    Roessler, E
    Traverso, G
    SiegelBartelt, J
    Frumkin, A
    Mitchell, HF
    DonisKeller, H
    Helms, C
    Hing, AV
    Heng, HHQ
    Koop, B
    Martindale, D
    Rommens, JM
    Tsui, LC
    Scherer, SW
    [J]. NATURE GENETICS, 1996, 14 (03) : 353 - 356
  • [6] Bellusci S, 1997, DEVELOPMENT, V124, P4867
  • [7] Sertoli cell signaling by Desert hedgehog regulates the male germline
    Bitgood, MJ
    Shen, LY
    McMahon, AP
    [J]. CURRENT BIOLOGY, 1996, 6 (03) : 298 - 304
  • [8] EFFECTS OF ALKALOIDS OF VERATRUM-CALIFORNICUM ON CHICK-EMBRYOS
    BRYDEN, MM
    PERRY, C
    KEELER, RF
    [J]. TERATOLOGY, 1973, 8 (01) : 19 - 27
  • [9] Chiang MK, 1996, DEVELOPMENT, V122, P2239
  • [10] Teratogen-mediated inhibition of target tissue response to Shh signaling
    Cooper, MK
    Porter, JA
    Young, KE
    Beachy, PA
    [J]. SCIENCE, 1998, 280 (5369) : 1603 - 1607