scholarly journals β1 Integrin regulates convergent extension in mouse notogenesis, ensures notochord integrity and the morphogenesis of vertebrae and intervertebral discs

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev192724
Author(s):  
Shiny Shengzhen Guo ◽  
Tiffany Y. K. Au ◽  
Sarah Wynn ◽  
Attila Aszodi ◽  
Danny Chan ◽  
...  

ABSTRACTThe notochord drives longitudinal growth of the body axis by convergent extension, a highly conserved developmental process that depends on non-canonical Wnt/planar cell polarity (PCP) signaling. However, the role of cell-matrix interactions mediated by integrins in the development of the notochord is unclear. We developed transgenic Cre mice, in which the β1 integrin gene (Itgb1) is ablated at E8.0 in the notochord only or in the notochord and tail bud. These Itgb1 conditional mutants display misaligned, malformed vertebral bodies, hemi-vertebrae and truncated tails. From early somite stages, the notochord was interrupted and displaced in these mutants. Convergent extension of the notochord was impaired with defective cell movement. Treatment of E7.25 wild-type embryos with anti-β1 integrin blocking antibodies, to target node pit cells, disrupted asymmetric localization of VANGL2. Our study implicates pivotal roles of β1 integrin for the establishment of PCP and convergent extension of the developing notochord, its structural integrity and positioning, thereby ensuring development of the nucleus pulposus and the proper alignment of vertebral bodies and intervertebral discs. Failure of this control may contribute to human congenital spine malformations.

2021 ◽  
Author(s):  
Shinuo Weng ◽  
Robert J. Huebner ◽  
John B. Wallingford

AbstractConvergent extension is an evolutionarily conserved collective cell movement that elongates the body axis of all animals and is required for the morphogenesis of several organ systems. Decades of study have revealed two distinct mechanisms of cell movement during CE, one based on cell crawling and the other on junction contraction. How these two behaviors collaborate during CE is unknown. Here, using quantitative live cell imaging we show that these two modes act both independently and in concert during CE, but that cell movement is more effective when the two modes are simultaneously integrated. Based on these findings, we developed a novel computational model that for the first time treats crawling and contraction independently. This model not only confirmed the biomechanical efficacy of integrating the two modes but also revealed for the first time how the two modes are affected by cell adhesion. Prompted by our modeling, we show that disruption of cell adhesion by knockdown of the Arvcf catenin results in specific failure of integration of crawling with contraction. These data are significant for providing new biomechanical and cell biological insights into a fundamental morphogenetic process implicated in human neural tube defects and skeletal dysplasias.


2003 ◽  
Vol 25 (5) ◽  
pp. 15-17 ◽  
Author(s):  
Jill Urban ◽  
Sally Roberts

The intervertebral discs are the largest avascular tissues in the body. They link the vertebral bodies and are the major joints of the spine, providing flexibility to an otherwise rigid structure. These large tissues are maintained by only a small population of cells; the cell density is one of the lowest of any tissue in the body with one cell responsible for synthesizing and maintaining as much as 200 times its volume of matrix. The discs show signs of degenerative change very early in life, possibly because of the hostile environment that they encounter; their nutrient supply is precarious and they experience high mechanical loads. Although recent work indicates that much degeneration is genetically determined, interactions between genes and the physical environment appear to increase the risk of disc degeneration, which itself is associated with one of the most costly medical conditions in the Western world, back pain.


Bone ◽  
2021 ◽  
pp. 115972
Author(s):  
Abhinav Suri ◽  
Brandon C. Jones ◽  
Grace Ng ◽  
Nancy Anabaraonye ◽  
Patrick Beyrer ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jianbiao Xu ◽  
Leiming Zhang ◽  
Rongqiang Bu ◽  
Yankang Liu ◽  
Kai-Uwe Lewandrowski ◽  
...  

Abstract Background Spondylodiscitis is an unusual infectious disease, which usually originates as a pathogenic infection of intervertebral discs and then spreads to neighboring vertebral bodies. The objective of this study is to evaluate percutaneous debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis. Methods From January 2002 to May 2017, 23 patients with multilevel spondylodiscitis were treated with minimally invasive debridement and drainage procedures in our department. The clinical manifestations, evolution, and minimally invasive debridement and drainage treatment of this refractory vertebral infection were investigated. Results Of the enrolled patients, the operation time ranged from 30 minutes to 124 minutes every level with an average of 48 minutes. Intraoperative hemorrhage was minimal. The postoperative follow-up period ranged from 12 months to 6.5 years with an average of 3.7 years. There was no reactivation of infection in the treated vertebral segment during follow-up, but two patients with fungal spinal infection continued to progress by affecting adjacent segments prior to final resolution. According to the classification system of Macnab, one patient had a good outcome at the final follow-up, and the rest were excellent. Conclusions Minimally invasive percutaneous debridement and irrigation using intraoperative CT-Guide is an effective minimally invasive method for the treatment of multilevel spondylodiscitis.


1999 ◽  
Vol 77 (5) ◽  
pp. 409-420 ◽  
Author(s):  
Dolores Hangan-Steinman ◽  
Wai-chi Ho ◽  
Priti Shenoy ◽  
Bosco MC Chan ◽  
Vincent L Morris

It is well established that a biphasic relationship exists between the adhesive strength of β1 integrins and their ability to mediate cell movement. Thus, cell movement increases progressively with adhesive strength, but beyond a certain point of optimal interaction, cell movement is reduced with further increases in adhesive function. The interplay between the various kinase and phosphatase activities provides the balance in β1 integrin-mediated cell adhesion and migration. In the present study, the significance of protein tyrosine phosphatases (PTP) and ser/thr protein phosphatases (PP) in α4β1 and α5β1 integrin-mediated mouse melanoma B16F1 cell anchorage and migration on fibronectin was characterized using phosphatase inhibitors. At low fibronectin concentration, α5β1 functioned as the predominant receptor for cell movement; a role for α4β1 in B16F1 cell migration increased progressively with fibronectin concentration. Treatment of B16F1 cells with PTP inhibitors, sodium orthovanadate (Na3VO4) and phenylarsine oxide (PAO), or PP-1/2A inhibitor, okadaic acid (OA), abolished cell movement. Inhibition of cell movement by PAO and OA was associated by a reduction in the adhesive strength of α4β1 and α5β1. In contrast, treatment of B16F1 cells with Na3VO4 resulted in selective stimulation of the adhesive function of α5β1, but not α4β1. Therefore, our results demonstrate that (i) both PTP and PP-1/2A have roles in cell movement, (ii) modulation of cell movement by PTP and PP-1/2A may involve either a stimulation or reduction of β1 integrin adhesive strength, and (iii) distinct phosphatase-mediated signaling pathways for differential regulation of the various β1 integrins exist. Key words: phosphatases, integrins, cell movement, cell adhesion.


2008 ◽  
Vol 316 (2) ◽  
pp. 288-301 ◽  
Author(s):  
Ambra Pozzi ◽  
George Jarad ◽  
Gilbert W. Moeckel ◽  
Sergio Coffa ◽  
Xi Zhang ◽  
...  

2013 ◽  
Vol 46 (3) ◽  
pp. 173-177 ◽  
Author(s):  
Cristiano Gonzaga de Souza ◽  
Emerson Leandro Gasparetto ◽  
Edson Marchiori ◽  
Paulo Roberto Valle Bahia

Spondylodiscitis represents 2%–4% of all bone infections cases. The correct diagnosis and appropriate treatment can prevent complications such as vertebral collapse and spinal cord compression, avoiding surgical procedures. The diagnosis is based on characteristic clinical and radiographic findings and confirmed by blood culture and biopsy of the disc or the vertebra. The present study was developed with Clementino Fraga Filho University Hospital patients with histopathologically and microbiologically confirmed diagnosis of spondylodiscitis, submitted to magnetic resonance imaging of the affected regions. In most cases, pyogenic spondylodiscitis affects the lumbar spine. The following findings are suggestive of the diagnosis: segmental involvement; ill-defined abscesses; early intervertebral disc involvement; homogeneous vertebral bodies and intervertebral discs involvement. Tuberculous spondylodiscitis affects preferentially the thoracic spine. Most suggestive signs include: presence of well-defined and thin-walled abscess; multisegmental, subligamentous involvement; heterogeneous involvement of vertebral bodies; and relative sparing of intervertebral discs. The present pictorial essay is aimed at showing the main magnetic resonance imaging findings of pyogenic and tuberculous discitis.


2002 ◽  
Vol 2 ◽  
pp. 434-454 ◽  
Author(s):  
Jeffrey D. Axelrod ◽  
Helen McNeill

Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical–basal axes, referred to as Planar Cell Polarity (PCP). The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly,Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate toDrosophilaPCP signaling.


2018 ◽  
Vol 49 (2) ◽  
pp. 135-163
Author(s):  
Shiloh Whitney

Abstract While Merleau-Ponty’s Phenomenology of Perception relies on the descriptive register of the body proper, his Sorbonne lectures on child psychology investigate the genesis of the experience of a body as one’s own. I demonstrate the uniqueness of Merleau-Ponty’s account of the narcissistic affect and sociality involved in this developmental process, distinguishing his account vis-à-vis Wallon’s and Lacan’s studies of the mirror stage. I conclude that in Merleau-Ponty’s account, (1) the experience of the body proper is not singular, but encompasses a range of phenomenological variation; and (2) the genesis of the body proper is not confined to the mirror stage. The production of bodily boundaries is an ongoing process identified not only with its advent in childhood, but also with adult emotional life. The boundaries between inner and outer domains of perception are not merely discovered, but must be negotiated and cultivated in the intercorporeal affective dramas of adult life.


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