Apical ectodermal ridge regulates three principal axes of the developing limb
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Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) ISSN 1673-1581 (Print); ISSN 1862-1783 (Online) www.jzus.zju.edu.cn; www.springerlink.com E-mail: [email protected]
Review:
Apical ectodermal ridge regulates three principal axes of the developing limb* Guo-hao LIN1,2, Lan ZHANG†‡2 1 2
Centre for Anatomy and Human Identification, University of Dundee, Dundee DD1 5EH, UK
Collaborative Innovation Center for Sports Health Promotion, Shandong Sport University, Jinan 250102, China †
E-mail: [email protected]
Received May 31, 2020; Revision accepted Aug. 6, 2020; Crosschecked Sept. 8, 2020
Abstract: 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. Key words: Apical ectodermal ridge (AER); Limb development; Fibroblast growth factor (FGF); Zone of polarizing activity (ZPA) https://doi.org/10.1631/jzus.B2000285 CLC number: R321.5
1 Introduction Studies on vertebrate limb development are of great significance for the understanding of pattern formation and morphogenesis in embryology (Casanova et al., 2011; Rodriguez-Leon et al., 2013). A ‡
Corresponding author Project supported by the Key Research and Development Project of Shandong Province (No. 2017G006043), China ORCID: Lan ZHANG, https://orcid.org/0000-0002-4897-6569 © Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2020 *
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