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CLC number: R321.5

On-line Access: 2020-10-12

Received: 2020-05-31

Revision Accepted: 2020-08-06

Crosschecked: 2020-09-08

Cited: 0

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Citations:  Bibtex RefMan EndNote GB/T7714


Lan Zhang


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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.10 P.757-766


Apical ectodermal ridge regulates three principal axes of the developing limb

Author(s):  Guo-hao Lin, Lan Zhang

Affiliation(s):  Centre for Anatomy and Human Identification, University of Dundee, Dundee DD1 5EH, UK; more

Corresponding email(s):   zhanglan@sdpei.edu.cn

Key Words:  Apical ectodermal ridge (AER), Limb development, Fibroblast growth factor (FGF), Zone of polarizing activity (ZPA)

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Guo-hao Lin, Lan Zhang. Apical ectodermal ridge regulates three principal axes of the developing limb[J]. Journal of Zhejiang University Science B, 2020, 21(10): 757-766.

@article{title="Apical ectodermal ridge regulates three principal axes of the developing limb",
author="Guo-hao Lin, Lan Zhang",
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publisher="Zhejiang University Press & Springer",

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%T Apical ectodermal ridge regulates three principal axes of the developing limb
%A Guo-hao Lin
%A Lan Zhang
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000285

T1 - Apical ectodermal ridge regulates three principal axes of the developing limb
A1 - Guo-hao Lin
A1 - Lan Zhang
J0 - Journal of Zhejiang University Science B
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SP - 757
EP - 766
%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2000285

Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.



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