A Self-Regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning

被引：159

作者：

Benazet, Jean-Denis ^{[1
]}

Bischofberger, Mirko ^{[2
,3
]}

Tiecke, Eva ^{[1
]}

Goncalves, Alexandre ^{[1
]}

Martin, James F. ^{[4
]}

Zuniga, Aimee ^{[1
]}

Naef, Felix ^{[2
,3
]}

Zeller, Rolf ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland

[2] Swiss Inst Expt Canc Res, Computat Syst Biol Grp, Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland

[3] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[4] Texas A&M Univ, Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA

来源：

SCIENCE | 2009年 / 323卷 / 5917期

基金：

瑞士国家科学基金会;

关键词：

VERTEBRATE LIMB; BUD; EXPRESSION; ROBUSTNESS; OUTGROWTH; EXPANSION; MESODERM; BMP4; SHH; CRE;

D O I：

10.1126/science.1168755

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：

Embryogenesis depends on self- regulatory interactions between spatially separated signaling centers, but few of these are well understood. Limb development is regulated by epithelial- mesenchymal (e-m) feedback loops between sonic hedgehog ( SHH) and fibroblast growth factor ( FGF) signaling involving the bone morphogenetic protein ( BMP) antagonist Gremlin1 ( GREM1). By combining mouse molecular genetics with mathematical modeling, we showed that BMP4 first initiates and SHH then propagates e- m feedback signaling through differential transcriptional regulation of Grem1 to control digit specification. This switch occurs by linking a fast BMP4/ GREM1 module to the slower SHH/ GREM1/ FGF e- m feedback loop. This self- regulatory signaling network results in robust regulation of distal limb development that is able to compensate for variations by interconnectivity among the three signaling pathways.

引用

页码：1050 / 1053

页数：4

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