Vertebrate Limb Development: Moving from Classical Morphogen Gradients to an Integrated 4-Dimensional Patterning System

被引:106
作者
Benazet, Jean-Denis [1 ]
Zeller, Rolf [1 ]
机构
[1] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland
来源
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY | 2009年 / 1卷 / 04期
基金
瑞士国家科学基金会;
关键词
APICAL ECTODERMAL RIDGE; RETINOIC ACID SYNTHESIS; SONIC-HEDGEHOG; FEEDBACK LOOP; POLARIZING ACTIVITY; MOUSE LIMB; POSITIONAL INFORMATION; SPATIAL-DISTRIBUTION; DIGIT IDENTITY; CHICK-EMBRYO;
D O I
10.1101/cshperspect.a001339
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Awealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and APaxis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.
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页数:14
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共 74 条
[1]  
Ahn K, 2001, DEVELOPMENT, V128, P4449
[2]   Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning [J].
Ahn, S ;
Joyner, AL .
CELL, 2004, 118 (04) :505-516
[3]   Visualization of cartilage formation: Insight into cellular properties of skeletal progenitors and chondrodysplasia syndromes [J].
Barna, Maria ;
Niswander, Lee .
DEVELOPMENTAL CELL, 2007, 12 (06) :931-941
[4]   A Self-Regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning [J].
Benazet, Jean-Denis ;
Bischofberger, Mirko ;
Tiecke, Eva ;
Goncalves, Alexandre ;
Martin, James F. ;
Zuniga, Aimee ;
Naef, Felix ;
Zeller, Rolf .
SCIENCE, 2009, 323 (5917) :1050-1053
[5]   The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth [J].
Boulet, AM ;
Moon, AM ;
Arenkiel, BR ;
Capecchi, MR .
DEVELOPMENTAL BIOLOGY, 2004, 273 (02) :361-372
[6]   Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression [J].
Capellini, Terence D. ;
Di Giacomo, Giuseppina ;
Salsi, Valentina ;
Brendolan, Andrea ;
Ferretti, Elisabetta ;
Srivastava, Deepak ;
Zappavigna, Vincenzo ;
Selleri, Licia .
DEVELOPMENT, 2006, 133 (11) :2263-2273
[7]   Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates [J].
Chen, MH ;
Li, YJ ;
Kawakami, T ;
Xu, SM ;
Chuang, PT .
GENES & DEVELOPMENT, 2004, 18 (06) :641-659
[8]   Manifestation of the limb prepattern: Limb development in the absence of sonic hedgehog function [J].
Chiang, C ;
Litingtung, Y ;
Harris, MP ;
Simandl, BK ;
Li, Y ;
Beachy, PA ;
Fallon, JF .
DEVELOPMENTAL BIOLOGY, 2001, 236 (02) :421-435
[9]   Developmental biology - Giving limbs a hand [J].
Cohn, MJ .
NATURE, 2000, 406 (6799) :953-954
[10]   Interdigital regulation of digit identity and homeotic transformation by modulated BMP signaling [J].
Dahn, RD ;
Fallon, JF .
SCIENCE, 2000, 289 (5478) :438-441