scholarly journals SOXC proteins amplify canonical WNT signaling to secure nonchondrocytic fates in skeletogenesis

2014 ◽  
Vol 207 (5) ◽  
pp. 657-671 ◽  
Author(s):  
Pallavi Bhattaram ◽  
Alfredo Penzo-Méndez ◽  
Kenji Kato ◽  
Kaustav Bandyopadhyay ◽  
Abhilash Gadi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Wnt Signaling ◽  
Cell Fate ◽  
Mouse Embryo ◽  
Limb Bud ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Canonical Wnt Signaling ◽  
Limiting Step ◽  
Canonical Wnt

Canonical WNT signaling stabilizes β-catenin to determine cell fate in many processes from development onwards. One of its main roles in skeletogenesis is to antagonize the chondrogenic transcription factor SOX9. We here identify the SOXC proteins as potent amplifiers of this pathway. The SOXC genes, i.e., Sox4, Sox11, and Sox12, are coexpressed in skeletogenic mesenchyme, including presumptive joints and perichondrium, but not in cartilage. Their inactivation in mouse embryo limb bud caused massive cartilage fusions, as joint and perichondrium cells underwent chondrogenesis. SOXC proteins govern these cells cell autonomously. They replace SOX9 in the adenomatous polyposis coli–Axin destruction complex and therein inhibit phosphorylation of β-catenin by GSK3. This inhibition, a crucial, limiting step in canonical WNT signaling, thus becomes a constitutive event. The resulting SOXC/canonical WNT-mediated synergistic stabilization of β-catenin contributes to efficient repression of Sox9 in presumptive joint and perichondrium cells and thereby ensures proper delineation and articulation of skeletal primordia. This synergy may determine cell fate in many processes besides skeletogenesis.

MicroRNA-663 activates the canonical Wnt signaling through the adenomatous polyposis coli suppression

2015 ◽  
Vol 166 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Cheng-gui Miao ◽  
Wei-jing Shi ◽  
You-yi Xiong ◽  
Hao Yu ◽  
Xiao-lin Zhang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Adenomatous Polyposis Coli ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

Establishment of the Axial Polarity and Cell Fate in Metazoa via Canonical Wnt Signaling: New Insights from Sponges and Annelids

2019 ◽  
Vol 46 (1) ◽  
pp. 14-25 ◽  
Author(s):  
V. V. Kozin ◽  
I. E. Borisenko ◽  
R. P. Kostyuchenko
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals The Microphthalmia-Associated Transcription Factor Mitf Interacts with β-Catenin To Determine Target Gene Expression

2006 ◽  
Vol 26 (23) ◽  
pp. 8914-8927 ◽  
Author(s):  
Alexander Schepsky ◽  
Katja Bruser ◽  
Gunnar J. Gunnarsson ◽  
Jane Goodall ◽  
Jón H. Hallsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Critical Role ◽  
Wnt Signaling Pathway ◽  
Feedback Mechanism ◽  
Canonical Wnt Signaling ◽  
Melanocyte Stem Cells ◽  
Canonical Wnt

ABSTRACT Commitment to the melanocyte lineage is characterized by the onset of expression of the microphthalmia-associated transcription factor (Mitf). This transcription factor plays a fundamental role in melanocyte development and maintenance and seems to be crucial for the survival of malignant melanocytes. Furthermore, Mitf has been shown to be involved in cell cycle regulation and to play important functions in self-renewal and maintenance of melanocyte stem cells. Although little is known about how Mitf regulates these various processes, one possibility is that Mitf interacts with other regulators. Here we show that Mitf can interact directly with β-catenin, the key mediator of the canonical Wnt signaling pathway. The Wnt signaling pathway plays a critical role in melanocyte development and is intimately involved in triggering melanocyte stem cell proliferation. Significantly, constitutive activation of this pathway is a feature of a number of cancers including malignant melanoma. Here we show that Mitf can redirect β-catenin transcriptional activity away from canonical Wnt signaling-regulated genes toward Mitf-specific target promoters to activate transcription. Thus, by a feedback mechanism, Mitf can diversify the output of canonical Wnt signaling to enhance the repertoire of genes regulated by β-catenin. Our results reveal a novel mechanism by which Wnt signaling and β-catenin activate gene expression, with significant implications for our understanding of both melanocyte development and melanoma.

scholarly journals Sox2 and canonical Wnt signaling interact to activate a developmental checkpoint coordinating morphogenesis with mesodermal fate acquisition

2020 ◽  
Author(s):  
Brian A. Kinney ◽  
Richard H. Row ◽  
Yu-Jung Tseng ◽  
Maxwell D. Weidmann ◽  
Holger Knaut ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Epithelial To Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Mesoderm Induction ◽  
Cell Fate Specification ◽  
Canonical Wnt Signaling ◽  
Mesodermal Cell ◽  
Mesenchymal Transition ◽  
Canonical Wnt

AbstractAnimal embryogenesis requires a precise coordination between morphogenesis and cell fate specification. It is unclear if there are mechanisms that prevent uncoupling of these processes to ensure robust development. During mesoderm induction, mesodermal fate acquisition is tightly coordinated with the morphogenetic process of epithelial to mesenchymal transition (EMT). In zebrafish, cells exist transiently in a partial EMT state during mesoderm induction. Here we show that cells expressing the neural inducing transcription factor Sox2 are held in the partial EMT state, stopping them from completing the EMT and joining the mesodermal territory. This is critical for preventing ectopic neural tissue from forming. The mechanism involves specific interactions between Sox2 and the mesoderm inducing canonical Wnt signaling pathway. When Wnt signaling is inhibited in Sox2 expressing cells trapped in the partial EMT, cells are now able to exit into the mesodermal territory, but form an ectopic spinal cord instead of mesoderm. Our work identifies a critical developmental checkpoint that ensures that morphogenetic movements establishing the mesodermal germ layer are accompanied by robust mesodermal cell fate acquisition.

scholarly journals Canonical Wnt Signaling Promotes Neovascularization Through Determination of Endothelial Progenitor Cell Fate via Metabolic Profile Regulation

Stem Cells ◽  
2019 ◽  
Vol 37 (10) ◽  
pp. 1331-1343 ◽  
Author(s):  
Yan Shao ◽  
Jianglei Chen ◽  
Willard Freeman ◽  
Li-Jie Dong ◽  
Zhi-Hui Zhang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Endothelial Progenitor Cell ◽  
Metabolic Profile ◽  
Progenitor Cell ◽  
Canonical Wnt Signaling ◽  
Endothelial Progenitor ◽  
Canonical Wnt

scholarly journals Non-Canonical Wnt Signaling and N-Cadherin Related β-Catenin Signaling Play a Role in Mechanically Induced Osteogenic Cell Fate

PLoS ONE ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. e5388 ◽  
Author(s):  
Emily J. Arnsdorf ◽  
Padmaja Tummala ◽  
Christopher R. Jacobs
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Osteogenic Cell ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt
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