John Saunders' ZPA, Sonic hedgehog and digit identity – How does it really all work?

Zhu, Jianjian; Mackem, Susan

doi:10.1016/j.ydbio.2017.02.001

Cited by 25 publications

(24 citation statements)

References 128 publications

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“…Proximal and distal radials, i.e., the fin endoskeleton, are considered homologous to the tetrapod limb endoskeleton [6, 7], and the process and mechanism of their patterning in embryonic development are similar to those of tetrapod limb development. During development, both paired fin radials and the limb endoskeleton are structured from the fin/limb bud containing two signaling centers, the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA), which are located at the dorsoventral border of the ectoderm and in the posterior mesenchyme, respectively [7–10]. The AER and ZPA secrete signaling molecules, and direct expression of patterning genes and establish morphology along the PD and AP axes in the fin/limb bud.…”

Section: Introductionmentioning

confidence: 99%

Pattern of fin rays along the antero-posterior axis based on their connection to distal radials

Hamada¹,

Uemoto²,

Tanaka³

et al. 2019

Zoological Lett

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Background Teleost paired fins are composed of two endoskeletal domains, proximal and distal radials, and an exoskeletal domain, the fin ray. The zebrafish pectoral fin displays elaborately patterned radials along the anteroposterior (AP) axis. Radials are considered homologous to tetrapod limb skeletons, and their patterning mechanisms in embryonic development are similar to those of limb development. Nevertheless, the pattern along the AP axis in fin rays has not been well described in the zebrafish pectoral fin, although several recent reports have revealed that fin ray development shares some cellular and genetic properties with fin/limb endoskeleton development. Thus, fin ray morphogenesis may involve developmental mechanisms for AP patterning in the fin/limb endoskeleton, and may have a specific pattern along the AP axis. Results We conducted detailed morphological observations on fin rays and their connection to distal radials by comparing intra- and inter-strain zebrafish specimens. Although the number of fin rays varied, pectoral fin rays could be categorized into three domains along the AP axis, according to the connection between the fin rays and distal radials; additionally, the number of fin rays varied in the posterior part of the three domains. This result was confirmed by observation of the morphogenesis process of fin rays and distal radials, which showed altered localization of distal radials in the middle domain. We also evaluated the expression pattern of lhx genes, which have AP patterning activity in limb development, in fin rays and during distal radial development and found these genes to be expressed during morphogenesis in both fin rays and distal radials. Conclusion The fin ray and its connection to the endoskeleton are patterned along the AP axis, and the pattern along the AP axis in the fin ray and the radial connection is constructed by the developmental mechanism related to AP patterning in the limb/fin bud. Our results indicate the possibility that the developmental mechanisms of fin rays and their connection are comparable to those of the distal element of the limb skeleton.

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Section: Introductionmentioning

confidence: 99%

Pattern of fin rays along the antero-posterior axis based on their connection to distal radials

Hamada¹,

Uemoto²,

Tanaka³

et al. 2019

Zoological Lett

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“…Shh serves as the P morphogen for all vertebrate limbs, and the feedback loop between Shh and Fgf8 also appears to be universal (Zhu & Mackem, 2017). However, the exact role of Fgf8 varies among taxa: salamanders express it in their anterior mesenchyme (Tanaka, 2016), while birds and mammals express it in apical (distal) ectoderm within the apical ectodermal ridge (Vogt & Duboule, 1999).…”

Section: A Plague Of Extra-legged Frogsmentioning

confidence: 99%

“…(c)) in cross-section (oval) on a salamander viewed from the side, with black and white indicating P and A domains. Outgrowth is governed by a positive feedback loop between Shh and Fgf8 mediated by Grem1 (Tanaka, 2016;Zhu & Mackem, 2017). Grem1 belongs to a different (BMP) signaling pathway (Vogt & Duboule, 1999).…”

Section: Frogs Appear To Represent a Compromise Situation In Bothmentioning

confidence: 99%

Reflections on Bateson's rule: Solving an old riddle about why extra legs are mirror‐symmetric

Held

Sessions

2019

J Exp Zool Pt B

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William Bateson was an obsessive observer of animal oddities, and at some point in his herculean survey of museum collections leading up to his monumental 1894 monograph (Materials for the study of variation), he noticed a peculiar trend among the preserved specimens (mainly insects) that possessed extra legs: multiple legs that branched from the same socket tended to be mirror images of their adjacent neighbors. He did not know why. These symmetry relationships have come to be known as Bateson's rule, and they have defied a satisfactory explanation for 125 years. In the past few decades, tantalizing clues have emerged from various lines of investigation, and those lines have converged on a possible solution. An attempt is made here to fit all of those clues together to form a coherent picture of the etiology. Two case studies have proven to be pivotal: a fly mutant whose extra legs are caused by patches of dying cells and a frog syndrome whose extra legs are caused by a parasitic flatworm. The conclusion reached is that the extra legs of insects and vertebrates obey Bateson's rule for the same reason, but that reason has nothing to do with the specific molecules in their signaling pathways. Rather, it is an emergent property of the circuitry of the pathways and their polarized alignments along the limb axes. A parade of theoretical models have tried and failed to crack this mystery in the past, and they are reviewed here as part of the narrative.

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“…Shh is called a morphogen since the signal of this ligand relies on its concentration [77]. The Shh is produced from zone of polarizing activity (ZPA), which is located on the posterior side of the limb bud in the embryo [78]. The Hedgehog pathway has a link with the formation of specific types of humans cancer [74].…”

Section: Canonical Hedgehog Pathwaymentioning

confidence: 99%

γ-Tocotrienol Reversal of Epithelial-to-Mesenchymal Transition in Human Breast Cancer Cells is Mediated through a Suppression of Canonical Wnt and Hedgehog Signaling

Ahmed¹,

Sylvester²

2018

Vitamin E in Health and Disease

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γ-Tocotrienol, a natural isoform within the vitamin E family of compounds, displays potent antiproliferative, apoptotic and reversal of epithelial-to-mesenchymal transition (EMT) activity against breast cancer using treatment doses that have little or no effect on normal cell viability. EMT is a route by which epithelial cells undergo various biochemical alterations leading to the acquisition of mesenchymal traits. Several aberrant signaling pathways are involved in EMT-dependent cancer metastasis. Specifically, dysregulation of the canonical Wnt and Hedgehog pathways are intimately involved in promoting breast cancer EMT and metastasis. Therefore, studies were conducted to examine effects of γ-tocotrienol on Wnt and Hedgehog signaling. Results from these studies demonstrate that γ-tocotrienol significantly inhibits canonical Wnt and Hedgehog signaling by inhibiting receptors, co-receptors and ligand expression, as well as inhibiting expression of cytosolic and nuclear signaling proteins within these pathways. Additional studies showed that γ-tocotrienol treatment increased the expression of negative regulators of both the Wnt and Hedgehog pathways. These findings demonstrate that γ-tocotrienol reversal of EMT is mediated, at least in part, through the inhibition of canonical Wnt and Hedgehog signaling, and strongly suggest that this form of vitamin E may provide significant benefit in the prevention and treatment of metastatic breast cancer.

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John Saunders' ZPA, Sonic hedgehog and digit identity – How does it really all work?

Cited by 25 publications

References 128 publications

Pattern of fin rays along the antero-posterior axis based on their connection to distal radials

Pattern of fin rays along the antero-posterior axis based on their connection to distal radials

Reflections on Bateson's rule: Solving an old riddle about why extra legs are mirror‐symmetric

γ-Tocotrienol Reversal of Epithelial-to-Mesenchymal Transition in Human Breast Cancer Cells is Mediated through a Suppression of Canonical Wnt and Hedgehog Signaling

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