scholarly journals Anterior expansion and posterior addition to the notochord mechanically coordinate embryo axis elongation

Development ◽  
2021 ◽  
Author(s):  
Susannah B.P. McLaren ◽  
Benjamin J. Steventon

How force generated by the morphogenesis of one tissue impacts the morphogenesis of other tissues to achieve an elongated embryo axis is not well understood. The notochord runs along the length of the somitic compartment and is flanked on either side by somites. Vacuolating notochord cells undergo a constrained expansion, increasing notochord internal pressure and driving its elongation and stiffening. Therefore, the notochord is appropriately positioned to play a role in mechanically elongating the somitic compartment. We use multi-photon cell ablation to remove specific regions of the notochord and quantify the impact on axis elongation. We show that anterior expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues, contributing to the elongation of segmented tissue during post-tailbud stages. Unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for stress generation along the AP axis. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo AP axis.

2021 ◽  
Author(s):  
Susannah B.P. McLaren ◽  
Benjamin J. Steventon

AbstractDuring development the embryo body progressively elongates from head-to-tail along the anterior-posterior (AP) axis. Multiple tissues contribute to this elongation through a combination of convergence and extension and/or volumetric growth. How force generated by the morphogenesis of one tissue impacts the morphogenesis of other axial tissues to achieve an elongated axis is not well understood. The notochord, a rod-shaped tissue possessed by all vertebrates, runs across the entire length of the somitic compartment and is flanked on either side by the developing somites in the segmented region of the axis and presomitic mesoderm in the posterior. Cells in the notochord undergo an expansion that is constrained by a stiff sheath of extracellular matrix, that increases the internal pressure in the notochord allowing it to straighten and elongate. Therefore, it is appropriately positioned to play a role in mechanically elongating the somitic compartment. Here, we use multi-photon mediated cell ablation to remove specific regions of the developing notochord and quantify the impact on axis elongation. We show that anterior notochord cell expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues and contributes to the elongation of segmented tissue during post-tailbud stages of development. Crucially, unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for force generation across the AP axis. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo AP axis.


Author(s):  
Ali Salehi ◽  
Armin Rahmatfam ◽  
Mohammad Zehsaz

The present study aimed to study ratcheting strains of corroded stainless steel 304LN elbow pipes subjected to internal pressure and cyclic bending moment. To this aim, spherical and cubical shapes corrosion are applied at two depths of 1 mm and 2 mm in the critical points of elbow pipe such as symmetry sites at intrados, extrados, and crown positions. Then, a Duplex 2205 stainless steel elbow pipe is considered as an alternative to studying the impact of the pipe materials, due to its high corrosion resistance and strength, toughness, and most importantly, the high fatigue strength and other mechanical properties than stainless steel 304LN. In order to perform numerical analyzes, the hardening coefficients of the materials were calculated. The results highlight a significant relationship between the destructive effects of corrosion and the depth and shape of corrosion, so that as corrosion increases, the resulting destructive effects increases as well, also, the ratcheting strains in cubic corrosions have a higher growth rate than spherical corrosions. In addition, the growth rate of the ratcheting strains in the hoop direction is much higher across the studied sample than the axial direction. The highest growth rate of hoop strain was observed at crown and the highest growth rate of axial strains occurred at intrados position. Altogether, Duplex 2205 material has a better performance than SS 304LN.


2020 ◽  
Author(s):  
Paco Lopez-Cuevas ◽  
Luke Deane ◽  
Yushi Yang ◽  
Chrissy L Hammond ◽  
Erika Kague

Notochordal cells play a pivotal role in vertebral column patterning, contributing to the formation of the inner architecture of intervertebral discs (IVDs). Their disappearance during development has been associated with reduced repair capacity and IVD degeneration. Notochordal remnants are known to cause chordomas, a highly invasive bone cancer associated with late diagnosis. Understanding the impact of neoplastic cells during development and on the surrounding vertebral column could open avenues for earlier intervention and therapeutics. We investigated the impact of transformed notochord cells in the zebrafish skeleton using a RAS expressing line in the notochord under the control of the Kita promoter, with the advantage of adulthood endurance. Transformed cells caused damage in the notochord and destabilised the sheath layer triggering a wound repair mechanism, with enrolment of sheath cells (col9a2+) and expression of wt1b, similar to induced notochord wounds. Moreover, increased recruitment of neutrophils and macrophages, displaying abnormal behaviour in proximity to the notochord sheath and transformed cells, supported parallels between chordomas, wound and inflammation. Cancerous notochordal cells interfere with differentiation of sheath cells to form chordacentra domains leading to fusions and vertebral clefts during development. Adults displayed IVD irregularities reminiscent of degeneration; reduced bone mineral density, increased osteoclast activity; while disorganised osteoblasts and collagen indicate impaired bone homeostasis. By depleting inflammatory cells, we abrogated chordoma development and rescued the skeletal features of the vertebral column. Therefore, we showed that transformed notochord cells alter the skeleton during life, causing a wound-like phenotype and activating chronic wound response, suggesting parallels between chordoma, wound, IVD degeneration and inflammation, highlighting inflammation as a promising target for future therapeutics.


2020 ◽  
Vol 117 (10) ◽  
pp. 3018-3028 ◽  
Author(s):  
Arman Amini ◽  
Vincent Wiegmann ◽  
Hamza Patel ◽  
Farlan Veraitch ◽  
Frank Baganz

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.


Author(s):  
Jing Lu ◽  
Frank Ma ◽  
Zhimin Tan ◽  
Terry Sheldrake

An unbonded flexible pipe typically consists of multiple metallic and thermoplastic layers, where each layer is designed to provide a specific structural function. The burst resistance against the internal pressure in an unbonded flexible pipe is provided mainly by its Flexlok layer. The Flexlok is made by helically-wound steel wires, with neighbouring wires interlocking each other. Beneath the Flexlok is the Flexbarrier, a polymer layer, acting as the boundary for conveyed fluids. The internal pressure is passed onto the Flexlok through the Flexbarrier layer. Under internal pressure, the Flexbarrier can creep into the gaps between Flexlok wires. Theoretically, the polymer material ingress could reduce the flexibility of the Flexlok due to premature lock-up between Flexlok wires and subsequently increase the stress levels. This study presents a 3D finite element analysis model developed to quantify the stress elevation in the Flexlok wire, caused by the Flexbarrier layer ingress. In terms of Flexlok gap size distribution, both nominal and worst case scenarios are studied. In the nominal scenario, the Flexlok gap sizes are evenly distributed. In the worst case scenario, the Flexlok gap is assumed to be completely closed at one position while the gaps at the neighbouring positions are twice the nominal size. Flexbarrier ingress with different temperatures is also studied. Conclusions are obtained by analyzing the simulation results. The work presented is part of an ongoing research and development project.


2007 ◽  
Vol 45 (1) ◽  
pp. 179-188 ◽  
Author(s):  
Kathryn A. Bottonari ◽  
John E. Roberts ◽  
Morgen A.R. Kelly ◽  
Todd B. Kashdan ◽  
Jeffrey A. Ciesla

2021 ◽  
pp. dmm.047001
Author(s):  
Paco López-Cuevas ◽  
Luke Deane ◽  
Yushi Yang ◽  
Chrissy L Hammond ◽  
Erika Kague

Notochordal cells play a pivotal role in vertebral column patterning, contributing to the formation of the inner architecture of intervertebral discs (IVDs). Their disappearance during development has been associated with reduced repair capacity and IVD degeneration. Notochord cells can give rise to chordomas, a highly invasive bone cancer associated with late diagnosis. Understanding the impact of neoplastic cells during development and on the surrounding vertebral column could open avenues for earlier intervention and therapeutics. We investigated the impact of transformed notochord cells in the zebrafish skeleton using a RAS expressing line in the notochord under the control of the Kita promoter, with the advantage of adulthood endurance. Transformed cells caused damage in the notochord and destabilised the sheath layer triggering a wound repair mechanism, with enrolment of sheath cells (col9a2+) and expression of wt1b, similar to induced notochord wounds. Moreover, increased recruitment of neutrophils and macrophages, displaying abnormal behaviour in proximity to the notochord sheath and transformed cells, supported parallels between chordomas, wound and inflammation. Cancerous notochordal cells interfere with differentiation of sheath cells to form chordacentra domains leading to fusions and vertebral clefts during development. Adults displayed IVD irregularities reminiscent of degeneration; reduced bone mineral density, increased osteoclast activity; while disorganised osteoblasts and collagen indicate impaired bone homeostasis. By depleting inflammatory cells, we abrogated chordoma development and rescued the skeletal features of the vertebral column. Therefore, we showed that transformed notochord cells alter the skeleton during life, causing a wound-like phenotype and activating chronic wound response, suggesting parallels between chordoma, wound, IVD degeneration and inflammation, highlighting inflammation as a promising target for future therapeutics.


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