scholarly journals FoxH1 mediates a Grg4 and Smad2 dependent transcriptional switch in Nodal signaling during Xenopus mesoderm development

2016 ◽  
Vol 414 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Christine D. Reid ◽  
Aaron B. Steiner ◽  
Sergey Yaklichkin ◽  
Qun Lu ◽  
Shouwen Wang ◽  
...  
Keyword(s):  
Nodal Signaling ◽  
Mesoderm Development ◽  
Transcriptional Switch

scholarly journals Fast1 functions as a transcriptional switch for nodal signaling in Xenopus mesodermal development

2008 ◽  
Vol 319 (2) ◽  
pp. 524
Author(s):  
Aaron Steiner ◽  
Christine Reid ◽  
Sergey Yaklichkin ◽  
Qun Lu ◽  
Shouwen Wang ◽  
...  
Keyword(s):  
Nodal Signaling ◽  
Transcriptional Switch ◽  
Mesodermal Development

scholarly journals A dual function of FGF signaling in Xenopus left-right axis formation

2018 ◽  
Author(s):  
Isabelle Schneider ◽  
Jennifer Kreis ◽  
Axel Schweickert ◽  
Martin Blum ◽  
Philipp Vick
Keyword(s):  
Model Organisms ◽  
Dual Function ◽  
Axis Formation ◽  
Mesoderm Induction ◽  
Nodal Signaling ◽  
Fgf Signaling ◽  
Mesoderm Development ◽  
Flow Sensing ◽  
Early Gastrula

AbstractOrgan left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). While the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development are conserved, diverging results from different model organisms suggested a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel to FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca2+-branch is required for specification of the flow sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification, namely for generating and sensing of leftward flow. Moreover, our data show that FGF functions in LR asymmetric development are conserved across vertebrate species, from fish to mammals.

scholarly journals FoxH1 mediates a Groucho-Smad-dependent transcriptional switch for nodal signaling

2009 ◽  
Vol 331 (2) ◽  
pp. 482
Author(s):  
Daniel S. Kessler ◽  
Aaron B. Steiner ◽  
Christine D. Reid ◽  
Sergey Yaklichkin ◽  
Qun Lu ◽  
...  
Keyword(s):  
Nodal Signaling ◽  
Transcriptional Switch

scholarly journals PMN-MDSCs Enhance CTC Metastatic Properties through Reciprocal Interactions via ROS/Notch/Nodal Signaling

2019 ◽  
Vol 20 (8) ◽  
pp. 1916 ◽  
Author(s):  
Marc L. Sprouse ◽  
Thomas Welte ◽  
Debasish Boral ◽  
Haowen N. Liu ◽  
Wei Yin ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Receptor Expression ◽  
Cell Populations ◽  
Nodal Signaling ◽  
Breast Cancer Patients ◽  
Tumoricidal Activity ◽  
Notch Activation ◽  
Notch1 Receptor

Intratumoral infiltration of myeloid-derived suppressor cells (MDSCs) is known to promote neoplastic growth by inhibiting the tumoricidal activity of T cells. However, direct interactions between patient-derived MDSCs and circulating tumors cells (CTCs) within the microenvironment of blood remain unexplored. Dissecting interplays between CTCs and circulatory MDSCs by heterotypic CTC/MDSC clustering is critical as a key mechanism to promote CTC survival and sustain the metastatic process. We characterized CTCs and polymorphonuclear-MDSCs (PMN-MDSCs) isolated in parallel from peripheral blood of metastatic melanoma and breast cancer patients by multi-parametric flow cytometry. Transplantation of both cell populations in the systemic circulation of mice revealed significantly enhanced dissemination and metastasis in mice co-injected with CTCs and PMN-MDSCs compared to mice injected with CTCs or MDSCs alone. Notably, CTC/PMN-MDSC clusters were detected in vitro and in vivo either in patients’ blood or by longitudinal monitoring of blood from animals. This was coupled with in vitro co-culturing of cell populations, demonstrating that CTCs formed physical clusters with PMN-MDSCs; and induced their pro-tumorigenic differentiation through paracrine Nodal signaling, augmenting the production of reactive oxygen species (ROS) by PMN-MDSCs. These findings were validated by detecting significantly higher Nodal and ROS levels in blood of cancer patients in the presence of naïve, heterotypic CTC/PMN-MDSC clusters. Augmented PMN-MDSC ROS upregulated Notch1 receptor expression in CTCs through the ROS-NRF2-ARE axis, thus priming CTCs to respond to ligand-mediated (Jagged1) Notch activation. Jagged1-expressing PMN-MDSCs contributed to enhanced Notch activation in CTCs by engagement of Notch1 receptor. The reciprocity of CTC/PMN-MDSC bi-directional paracrine interactions and signaling was functionally validated in inhibitor-based analyses, demonstrating that combined Nodal and ROS inhibition abrogated CTC/PMN-MDSC interactions and led to a reduction of CTC survival and proliferation. This study provides seminal evidence showing that PMN-MDSCs, additive to their immuno-suppressive roles, directly interact with CTCs and promote their dissemination and metastatic potency. Targeting CTC/PMN-MDSC heterotypic clusters and associated crosstalks can therefore represent a novel therapeutic avenue for limiting hematogenous spread of metastatic disease.

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