The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

Haack, Timm; Abdelilah‐Seyfried, Salim

doi:10.1242/dev.131425

Cited by 84 publications

(74 citation statements)

References 192 publications

(231 reference statements)

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“…Zebrafish is emerging as an invaluable model system to study the influence of mechanical forces in cardiac valve formation [4][5][6][7][8]. In zebrafish, the atrioventricular (AV) valves emanate from the endocardial cells (EdCs) [9].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Complementary functions of the mechanosensitive factorsegr1,klf2bandklf2ainstruct the endocardial program

Faggianelli-Conrozier

Polyzou

Chow

et al. 2019

Preprint

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Mechanical forces are key modulators of valvulogenic developmental programs. However, the mechanosensitive gene network underlying this process remains unclear. It is well established that contractile and flow forces activate endocardial expression of the transcription factor klf2a during valve morphogenesis. We report two novel transcription factors with a function in heart valve formation in zebrafish: egr1 and klf2b. Genomewide analysis of gene expression reveals that the endocardial transcriptional programs modulated by klf2a, klf2b, and egr1 mainly contain non-redundant targets. Several of these targets have been implicated in endothelial-to-mesenchymal transition (EMT). VEGF receptor 1 (flt1) is a target of egr1 and klf2b during early valvulogenesis. These findings suggest that klf2a, klf2b, and egr1 cooperate for the activation of EMT program in response to mechanosensitive inputs. We propose that the combinatorial action of these factors mediates flow mechanotransduction to control the endocardial program, especially for valve development. Many of the deregulated genes exhibit changes in chromatin accessibility pointing to potential direct effects of these factors. Finally, in vivo phenotypic analyses show that

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Complementary functions of the mechanosensitive factorsegr1,klf2bandklf2ainstruct the endocardial program

Faggianelli-Conrozier

Polyzou

Chow

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…It is important for several biological processes including sensory perception like pain, 1 touch, 2 hearing, 3 and proprioception, 4 but also for embryonic development of tissues and organs. 5 Proprioception is the sensing of body part positioning and muscle stretch, which is mediated by mechanosensation in proprioceptors like muscle spindles in striated muscles or the Golgi tendon organs (GTOs) in tendons. 4 These structures sense mechanical forces like stretch or pressure upon their cell membranes via mechanically activated ion channels, and they propagate proprioceptive information via afferent nerve fibers.…”

mentioning

confidence: 99%

Biallelic Loss of Proprioception-Related PIEZO2 Causes Muscular Atrophy with Perinatal Respiratory Distress, Arthrogryposis, and Scoliosis

Vedove

Storbeck

Heller

et al. 2016

The American Journal of Human Genetics

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We report ten individuals of four independent consanguineous families from Turkey, India, Libya, and Pakistan with a variable clinical phenotype that comprises arthrogryposis, spontaneously resolving respiratory insufficiency at birth, muscular atrophy predominantly of the distal lower limbs, scoliosis, and mild distal sensory involvement. Using whole-exome sequencing, SNPchip-based linkage analysis, DNA microarray, and Sanger sequencing, we identified three independent homozygous frameshift mutations and a homozygous deletion of two exons in PIEZO2 that segregated in all affected individuals of the respective family. The mutations are localized in the N-terminal and central region of the gene, leading to nonsense-mediated transcript decay and consequently to lack of PIEZO2 protein. In contrast, heterozygous gain-of-function missense mutations, mainly localized at the C terminus, cause dominant distal arthrogryposis 3 (DA3), distal arthrogryposis 5 (DA5), or Marden-Walker syndrome (MWKS), which encompass contractures of hands and feet, scoliosis, ophthalmoplegia, and ptosis. PIEZO2 encodes a mechanosensitive ion channel that plays a major role in light-touch mechanosensation and has recently been identified as the principal mechanotransduction channel for proprioception. Mice ubiquitously depleted of PIEZO2 are postnatally lethal. However, individuals lacking PIEZO2 develop a not life-threatening, slowly progressive disorder, which is likely due to loss of PIEZO2 protein in afferent neurons leading to disturbed proprioception causing aberrant muscle development and function. Here we report a recessively inherited PIEZO2-related disease and demonstrate that depending on the type of mutation and the mode of inheritance, PIEZO2 causes clinically distinguishable phenotypes.

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“…Thus future work will delineate the direct and downstream mechanisms by which HspB5 affects adhesiveness, and how these may overlap with HspB1, which has a similar effect on the migration of NIH3T3 fibroblasts (Lee et al 2008). These mechanisms may also yield insight into the unclear physiological roles of sHSPs in development (Dubinska-Magiera et al 2014); a period when proper cell migration and positioning is heavily guided by mechanotransduction cues (Haack and Abdelilah-Seyfried 2016).…”

Section: Tension-related Functions Of Shspsmentioning

confidence: 98%

Small heat-shock proteins and their role in mechanical stress

Collier

Benesch

2020

Cell Stress and Chaperones

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The ability of cells to respond to stress is central to health. Stress can damage folded proteins, which are vulnerable to even minor changes in cellular conditions. To maintain proteostasis, cells have developed an intricate network in which molecular chaperones are key players. The small heat-shock proteins (sHSPs) are a widespread family of molecular chaperones, and some sHSPs are prominent in muscle, where cells and proteins must withstand high levels of applied force. sHSPs have long been thought to act as general interceptors of protein aggregation. However, evidence is accumulating that points to a more specific role for sHSPs in protecting proteins from mechanical stress. Here, we briefly introduce the sHSPs and outline the evidence for their role in responses to mechanical stress. We suggest that sHSPs interact with mechanosensitive proteins to regulate physiological extension and contraction cycles. It is likely that further study of these interactionsenabled by the development of experimental methodologies that allow protein contacts to be studied under the application of mechanical forcewill expand our understanding of the activity and functions of sHSPs, and of the roles played by chaperones in general.

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The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis

Cited by 84 publications

References 192 publications

WITHDRAWN: Complementary functions of the mechanosensitive factorsegr1,klf2bandklf2ainstruct the endocardial program

WITHDRAWN: Complementary functions of the mechanosensitive factorsegr1,klf2bandklf2ainstruct the endocardial program

Biallelic Loss of Proprioception-Related PIEZO2 Causes Muscular Atrophy with Perinatal Respiratory Distress, Arthrogryposis, and Scoliosis

Small heat-shock proteins and their role in mechanical stress

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