scholarly journals Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava

Biology Open ◽  
2015 ◽  
Vol 4 (7) ◽  
pp. 830-842 ◽  
Author(s):  
E. Rottinger ◽  
T. Q. DuBuc ◽  
A. R. Amiel ◽  
M. Q. Martindale
Keyword(s):  
Nodal Signaling ◽  
Ptychodera Flava

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.

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 Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo

2006 ◽  
Vol 295 (2) ◽  
pp. 743-755 ◽  
Author(s):  
Anne Camus ◽  
Aitana Perea-Gomez ◽  
Anne Moreau ◽  
Jérôme Collignon
Keyword(s):  
Mouse Embryo ◽  
Neural Differentiation ◽  
Nodal Signaling

scholarly journals Reversal of left-right asymmetry induced by aberrant Nodal signaling in the node of mouse embryos

Development ◽  
2009 ◽  
Vol 136 (23) ◽  
pp. 3917-3925 ◽  
Author(s):  
S. Oki ◽  
K. Kitajima ◽  
S. Marques ◽  
J. A. Belo ◽  
T. Yokoyama ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Nodal Signaling ◽  
Left Right Asymmetry

scholarly journals Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination

Development ◽  
2007 ◽  
Vol 134 (24) ◽  
pp. 4381-4393 ◽  
Author(s):  
C. V. Esguerra ◽  
L. Nelles ◽  
L. Vermeire ◽  
A. Ibrahimi ◽  
A. D. Crawford ◽  
...  
Keyword(s):  
Nodal Signaling

scholarly journals Primary cilium polarity: morphogenetic consequences.

2018 ◽  
Author(s):  
Marco Regolini
Keyword(s):  
Primary Cilia ◽  
Break Symmetry ◽  
Otic Vesicle ◽  
Nodal Signaling ◽  
Lateral Plate Mesoderm ◽  
Cell Orientation ◽  
Lateral Plate ◽  
Situs Solitus ◽  
Left And Right ◽  
Breaking Symmetry

In zebrafish inner ear, hair cell orientation in anterior and posterior maculae of the embryonic otic vesicle is different (about 30-40 degrees): this is rather unusual in planar polarity mechanism of action, instead suggests that kinocilia may be rotationally polarized. In mice node, the innermost monociliated cells generate a left-ward fluid flow sensed by the immotile primary cilia of Left peri-nodal cells: the Nodal signaling pathway is then expressed asymmetrically, in the Left lateral plate mesoderm, breaking symmetry in visceral organs (situs solitus); however, Right peri-nodal cells also, if artificially excited by a right-ward flow, break symmetry and activate the Nodal cascade, though inverting visceral organ asymmetry (situs inversus); surprisingly, peri-nodal cells prove to be adept at distinguishing flow directionality. Recently, in the Kupffer vesicle (the zebrafish laterality organ), chiral primary cilia orientation has been described: primary cilia, in the left and right side, are symmetrically oriented, showing a mirror average divergence of about 15-20 degrees from the midline. This finding, taken together with the mirror behavior of mouse perinodal cells and zebrafish hair cells, champions the idea of primary cilia enantiomerism.

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