Faculty Opinions recommendation of Fluid-dynamical basis of the embryonic development of left-right asymmetry in vertebrates.

Author(s):  
Manfred Schliwa
Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1756
Author(s):  
Jessica Guerra ◽  
Paola Chiodelli ◽  
Chiara Tobia ◽  
Claudia Gerri ◽  
Marco Presta

Primary cilium drives the left-right asymmetry process during embryonic development. Moreover, its dysregulation contributes to cancer progression by affecting various signaling pathways. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system modulates primary cilium length and plays a pivotal role in embryogenesis and tumor growth. Here, we investigated the impact of the natural FGF trap long-pentraxin 3 (PTX3) on the determination of primary cilium extension in zebrafish embryo and cancer cells. The results demonstrate that down modulation of the PTX3 orthologue ptx3b causes the shortening of primary cilium in zebrafish embryo in a FGF-dependent manner, leading to defects in the left-right asymmetry determination. Conversely, PTX3 upregulation causes the elongation of primary cilium in FGF-dependent cancer cells. Previous observations have identified the PTX3-derived small molecule NSC12 as an orally available FGF trap with anticancer effects on FGF-dependent tumors. In keeping with the non-redundant role of the FGF/FGR system in primary cilium length determination, NSC12 induces the elongation of primary cilium in FGF-dependent tumor cells, thus acting as a ciliogenic anticancer molecule in vitro and in vivo. Together, these findings demonstrate the ability of the natural FGF trap PTX3 to exert a modulatory effect on primary cilium in embryonic development and cancer. Moreover, they set the basis for the design of novel ciliogenic drugs with potential implications for the therapy of FGF-dependent tumors.


2016 ◽  
Vol 371 (1710) ◽  
pp. 20150413 ◽  
Author(s):  
Leo Q. Wan ◽  
Amanda S. Chin ◽  
Kathryn E. Worley ◽  
Poulomi Ray

Increasing evidence suggests that intrinsic cell chirality significantly contributes to the left–right (LR) asymmetry in embryonic development, which is a well-conserved characteristic of living organisms. With animal embryos, several theories have been established, but there are still controversies regarding mechanisms associated with embryonic LR symmetry breaking and the formation of asymmetric internal organs. Recently, in vitro systems have been developed to determine cell chirality and to recapitulate multicellular chiral morphogenesis on a chip. These studies demonstrate that chirality is indeed a universal property of the cell that can be observed with well-controlled experiments such as micropatterning. In this paper, we discuss the possible benefits of these in vitro systems to research in LR asymmetry, categorize available platforms for single-cell chirality and multicellular chiral morphogenesis, and review mathematical models used for in vitro cell chirality and its applications in in vivo embryonic development. These recent developments enable the interrogation of the intracellular machinery in LR axis establishment and accelerate research in birth defects in laterality. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.


2005 ◽  
Vol 13 (S2) ◽  
pp. 97-103 ◽  
Author(s):  
LEWIS WOLPERT

Symmetry across the midline is present in many animals, together with the left/right asymmetry of several organs, such as the heart in vertebrates. The development of such asymmetries during embryonic development requires first the specification of the midline and then specification of left/right. One model proposes the transfer of molecular asymmetry to the multicellular level. Nodal expression on the left side in mammals and chicks is a key event, and is due to the release of calcium on the left possibly involving an ion pump and the Notch pathway


2001 ◽  
Vol 7 (S2) ◽  
pp. 1012-1013
Author(s):  
Uyen Tram ◽  
William Sullivan

Embryonic development is a dynamic event and is best studied in live animals in real time. Much of our knowledge of the early events of embryogenesis, however, comes from immunofluourescent analysis of fixed embryos. While these studies provide an enormous amount of information about the organization of different structures during development, they can give only a static glimpse of a very dynamic event. More recently real-time fluorescent studies of living embryos have become much more routine and have given new insights to how different structures and organelles (chromosomes, centrosomes, cytoskeleton, etc.) are coordinately regulated. This is in large part due to the development of commercially available fluorescent probes, GFP technology, and newly developed sensitive fluorescent microscopes. For example, live confocal fluorescent analysis proved essential in determining the primary defect in mutations that disrupt early nuclear divisions in Drosophila melanogaster. For organisms in which GPF transgenics is not available, fluorescent probes that label DNA, microtubules, and actin are available for microinjection.


2014 ◽  
Vol 47 (06) ◽  
Author(s):  
N Bergemann ◽  
K Boyle ◽  
WE Paulus

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