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 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 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.

scholarly journals Author response: Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

2016 ◽  
Author(s):  
Megan L Norris ◽  
Andrea Pauli ◽  
James A Gagnon ◽  
Nathan D Lord ◽  
Katherine W Rogers ◽  
...  
Keyword(s):  
Cell Migration ◽  
Author Response ◽  
Nodal Signaling ◽  
Mesodermal Cell

scholarly journals Pig Epiblast Stem Cells Depend on Activin/Nodal Signaling for Pluripotency and Self-Renewal

2010 ◽  
Vol 19 (10) ◽  
pp. 1627-1636 ◽  
Author(s):  
Ramiro Alberio ◽  
Nicola Croxall ◽  
Cinzia Allegrucci
Keyword(s):  
Stem Cells ◽  
Nodal Signaling ◽  
Self Renewal ◽  
Epiblast Stem Cells
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