The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling

Cheong, Sek‐Shir; Akram, Khondoker M.; Matellan, Carlos; Kim, Sally Yunsun; Gaboriau, David; Hind, Matthew; Hernández, Armando E. del Río; Griffiths, Mark; Dean, Charlotte

doi:10.3389/fcell.2020.577201

Cited by 19 publications

(31 citation statements)

References 88 publications

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“…The impairments of these processes in Vangl2 Lp mice lead to a deficiency of the mechanoregulator YAP. The inactivation of Vangl2 is associated with a decrease in nuclear (active) YAP and an increase in cytoplasmic (inactive) phospho-YAP in the lung epithelium [176]. In utero, YAP and its nucleocytoplasmic shuttling are known to be crucial for lung branching morphogenesis [177,178], while TAZ deletion causes abnormalities in postnatal alveologenesis, leading to an emphysema-like phenotype in adult mice [179].…”

Section: Remodeling Of the Cell Cytoskeleton Is Necessary For Alveologenesismentioning

confidence: 99%

“…Previously, Park and colleagues found that YAP/TAZ transcription coactivators could act as downstream effectors of the PCP pathway, mediating cell migration through Frizzled and ROR receptors [180]. YAP provides the readout of mechanosignal activity [181,182], while Vangl2 is suggested to play an active role in mechanosignal transmission [176].…”

Section: Remodeling Of the Cell Cytoskeleton Is Necessary For Alveologenesismentioning

confidence: 99%

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Alveologenesis: What Governs Secondary Septa Formation

Алпеева

Vasiliev

Vorotelyak

2021

IJMS

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The simplification of alveoli leads to various lung pathologies such as bronchopulmonary dysplasia and emphysema. Deep insight into the process of emergence of the secondary septa during development and regeneration after pneumonectomy, and into the contribution of the drivers of alveologenesis and neo-alveolarization is required in an efficient search for therapeutic approaches. In this review, we describe the formation of the gas exchange units of the lung as a multifactorial process, which includes changes in the actomyosin cytoskeleton of alveocytes and myofibroblasts, elastogenesis, retinoic acid signaling, and the contribution of alveolar mesenchymal cells in secondary septation. Knowledge of the mechanistic context of alveologenesis remains incomplete. The characterization of the mechanisms that govern the emergence and depletion of αSMA will allow for an understanding of how the niche of fibroblasts is changing. Taking into account the intense studies that have been performed on the pool of lung mesenchymal cells, we present data on the typing of interstitial fibroblasts and their role in the formation and maintenance of alveoli. On the whole, when identifying cell subpopulations in lung mesenchyme, one has to consider the developmental context, the changing cellular functions, and the lability of gene signatures.

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Section: Remodeling Of the Cell Cytoskeleton Is Necessary For Alveologenesismentioning

confidence: 99%

Section: Remodeling Of the Cell Cytoskeleton Is Necessary For Alveologenesismentioning

confidence: 99%

Alveologenesis: What Governs Secondary Septa Formation

Алпеева

Vasiliev

Vorotelyak

2021

IJMS

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“…The promotion of cellular migration enhances angiogenesis and lymphangiogenesis, as well as tumor lymphatic metastasis [62][63][64]. Lymphangiogenesis could also be linked to Rho interaction with VANGL2, a key regulator of mechanotransduction and the planar-cell-polarity pathway [65]. As for the mechanism of action, several studies suggest that RhoA can be activated by different proteins encoded by the proposed candidate genes (ANGPTL4, CDH5, LPAR, PDPN, PLXNA1, S1PR, and SEMA3A), and it then activates its effector ROCK.…”

Section: Rho/rock Pathwaymentioning

confidence: 99%

“…PathVisio software was used for the creation of molecular pathway diagrams [115]. Of the 92 studies used for the creation of Supplementary Tables S1 and S2, 65 were not cited in the main article .…”

mentioning

confidence: 99%

Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways

Bonetti

Paolacci

Samaja³

et al. 2022

IJMS

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Lymphedema is a chronic inflammatory disorder caused by ineffective fluid uptake by the lymphatic system, with effects mainly on the lower limbs. Lymphedema is either primary, when caused by genetic mutations, or secondary, when it follows injury, infection, or surgery. In this study, we aim to assess to what extent the current genetic tests detect genetic variants of lymphedema, and to identify the major molecular pathways that underlie this rather unknown disease. We recruited 147 individuals with a clinical diagnosis of primary lymphedema and used established genetic tests on their blood or saliva specimens. Only 11 of these were positive, while other probands were either negative (63) or inconclusive (73). The low efficacy of such tests calls for greater insight into the underlying mechanisms to increase accuracy. For this purpose, we built a molecular pathways diagram based on a literature analysis (OMIM, Kegg, PubMed, Scopus) of candidate and diagnostic genes. The PI3K/AKT and the RAS/MAPK pathways emerged as primary candidates responsible for lymphedema diagnosis, while the Rho/ROCK pathway appeared less critical. The results of this study suggest the most important pathways involved in the pathogenesis of lymphedema, and outline the most promising diagnostic and candidate genes to diagnose this disease.

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“…However, YAP/TAZ target genes are not affected by the loss of Fat4 ( 58 ). VANGL2 is also a core PCP component and YAP activity is reduced in the lung airways of Vangl2 Lp embryos ( 59 ). Looptail embryos, Vangl2 mutants, possess lymphatic valve maturation defect ( 13 ).…”

Section: Upstream Signals Regulating Hippo-yap/taz Pathway In Lecsmentioning

confidence: 99%

A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development

Cha

Moon

Kim

2021

BMB Rep

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The lymphatic vasculature plays important role in regulating fluid homeostasis, intestinal lipid absorption, and immune surveillance in humans. Malfunction of lymphatic vasculature leads to several human diseases. Understanding the fundamental mechanism in lymphatic vascular development not only expand our knowledge, but also provide a new therapeutic insight. Recently, Hippo-YAP/TAZ signaling pathway, a key mechanism of organ size and tissue homeostasis, has emerged as a critical player that regulate lymphatic specification, sprouting, and maturation. In this review, we discuss the mechanistic regulation and pathophysiological significant of Hippo pathway in lymphatic vascular development. [

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The Planar Polarity Component VANGL2 Is a Key Regulator of Mechanosignaling

Cited by 19 publications

References 88 publications

Alveologenesis: What Governs Secondary Septa Formation

Alveologenesis: What Governs Secondary Septa Formation

Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways

A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development

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