Mechanisms of intercellular Wnt transport

Routledge, Daniel; Scholpp, Steffen

doi:10.1242/dev.176073

Cited by 129 publications

(111 citation statements)

References 127 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…We find that overexpression of Gsk3β leads to an expansion of the forebrain primordium (FBP) including the eye field and midbrain primordium (MBP) at the expense of the hindbrain primordium (HBP) ( Fig 2F; (n = 8/10) compared to embryos injected with the same amount of control mRNA (Fig 2E, n = 10/10). This finding is following the observation that reducing β-catenin level leads to an anteriorization of the neural plate (reviewed in [25]). The boundary between the forebrain and the midbrain primordium shifts towards the posterior; however, we observed no alteration of the sharpness of the border.…”

Section: Plos Computational Biologysupporting

confidence: 59%

Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

et al. 2020

Self Cite

View full text Add to dashboard Cite

During embryogenesis, morphogens form a concentration gradient in responsive tissue, which is then translated into a spatial cellular pattern. The mechanisms by which morphogens spread through a tissue to establish such a morphogenetic field remain elusive. Here, we investigate by mutually complementary simulations and in vivo experiments how Wnt morphogen transport by cytonemes differs from typically assumed diffusion-based transport for patterning of highly dynamic tissue such as the neural plate in zebrafish. Stochasticity strongly influences fate acquisition at the single cell level and results in fluctuating boundaries between pattern regions. Stable patterning can be achieved by sorting through concentration dependent cell migration and apoptosis, independent of the morphogen transport mechanism. We show that Wnt transport by cytonemes achieves distinct Wnt thresholds for the brain primordia earlier compared with diffusion-based transport. We conclude that a cytoneme-mediated morphogen transport together with directed cell sorting is a potentially favored mechanism to establish morphogen gradients in rapidly expanding developmental systems.

show abstract

Section: Plos Computational Biologysupporting

confidence: 59%

Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Wnt signaling network comprises several signaling pathways, of which the best studied are the canonical Wnt/β-catenin pathway and noncanonical Wnt/PCP-JNK pathway [ 28 ]. These two pathways are primarily thought to act in a mutually repressive manner because they compete for common proteins, such as the scaffolding protein disheveled [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway

Liu

et al. 2020

Acta Pharmacol Sin

View full text Add to dashboard Cite

Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Wnt/β-catenin signaling in Dox-induced cardiotoxicity. Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling. In this study, we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo. We showed that treatment of H9c2 cardiac myoblasts with Dox (1 μM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling. Pretreatment with SP600125, the Wnt/PCP-JNK signaling inhibitor, attenuated Dox-induced apoptosis of H9c2 cells. Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox, rats displayed significant cardiac dysfunction; their heart showed inhibited Wnt/β-catenin signaling and activated Wnt/PCP-JNK signaling. These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity.

show abstract

“…Interestingly, our data show that different levels of Awd elicit different effect on key signal transduction pathways such as Notch and Wg. Moreover, Wg signaling requires different transport mechanisms that are context- and tissue-specific [ 42 ]. Further studies of the cellular effects arising from awd downregulation could help in understanding the complex functions played by NME1/2 proteins.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Drosophila Awd/NME1/2 Levels on Notch and Wg Signaling Pathways

Serafini

Giordani

Grillini

et al. 2020

IJMS

View full text Add to dashboard Cite

Awd, the Drosophila homologue of NME1/2 metastasis suppressors, plays key roles in many signaling pathways. Mosaic analysis of the null awdJ2A4 allele showed that loss of awd gene function blocks Notch signaling and the expression of its target genes including the Wingless (Wg/Wnt1) morphogen. We also showed that RNA interference (RNAi)-mediated awd silencing (awdi) in larval wing disc leads to chromosomal instability (CIN) and to Jun amino-terminal kinases (JNK)-mediated cell death. Here we show that this cell death is independent of p53 activity. Based on our previous finding showing that forced survival of awdi-CIN cells leads to aneuploidy without the hyperproliferative effect, we investigated the Wg expression in awdi wing disc cells. Interestingly, the Wg protein is expressed in its correct dorso-ventral domain but shows an altered cellular distribution which impairs its signaling. Further, we show that RNAi-mediated knock down of awd in wing discs does not affect Notch signaling. Thus, our analysis of the hypomorphic phenotype arising from awd downregulation uncovers a dose-dependent effect of Awd in Notch and Wg signaling.

show abstract

Mechanisms of intercellular Wnt transport

Cited by 129 publications

References 127 publications

Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway

The Impact of Drosophila Awd/NME1/2 Levels on Notch and Wg Signaling Pathways

Contact Info

Product

Resources

About