Breaking Left–Right Symmetry by the Interplay of Planar Cell Polarity, Calcium Signaling and Cilia DOI Creative Commons

De‐Li Shi

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2116 - 2116

Published: Dec. 20, 2024

The formation of the embryonic left–right axis is a fundamental process in animals, which subsequently conditions both shape and correct positioning internal organs. During vertebrate early development, transient structure, known as organizer, breaks bilateral symmetry manner that critically dependent on activity motile immotile cilia or asymmetric cell migration. Extensive studies have partially elucidated molecular pathways initiate patterning morphogenesis. Wnt/planar polarity signaling plays an important role biased orientation rotational motion cilia. leftward fluid flow generated cavity organizer sensed by through complex mechanisms to trigger left-sided calcium lateralized gene expression pattern. Disrupted impaired structure function leads randomized determination, closely linked laterality defects, particularly congenital heart disease. Despite formidable progress made deciphering critical contribution establishing asymmetry, strong challenge remains understand how generate sense differentially activate across axis. This review analyzes underlying morphogenesis formation. It also aims identify questions are open for future investigations.

Language: Английский

The Function of Circular RNAs in Regulating Wnt/β-Catenin Signaling: An Innovative Therapeutic Strategy for breast and gynecological Cancers DOI

Samaneh Kahkesh,

Neda Hedayati,

Payman Rahimzadeh

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155944 - 155944

Published: March 1, 2025

Language: Английский

Citations

1
Wnt Pathway-Targeted Therapy in Gastrointestinal Cancers: Integrating Benchside Insights with Bedside Applications DOI Creative Commons
Ashok Kumar Nayak,

Hannah Streiff,

Iván González

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 178 - 178

Published: Jan. 24, 2025

The Wnt signaling pathway is critical in the onset and progression of gastrointestinal (GI) cancers. Anomalies this pathway, often stemming from mutations components such as adenomatous polyposis coli (APC) or β-catenin, lead to uncontrolled cell proliferation survival. In case colorectal cancer, dysregulation drives tumor initiation growth. Similarly, aberrant contributes development, metastasis, resistance therapy other GI cancers, gastric, pancreatic, hepatocellular carcinomas. Targeting its downstream effectors has emerged a promising therapeutic strategy for combating these highly aggressive malignancies. Here, we review pathogenesis cancers further explore potential targeting various pathway. Furthermore, summarize integrate preclinical evidence supporting efficacy potent inhibitors with completed ongoing clinical trials Additionally, discuss challenges pathway-targeted therapies overcome concerns effective translation.

Language: Английский

Citations

0
Anti-resonance in developmental signaling regulates cell fate decisions DOI Creative Commons
Samuel J Rosen, Olivier Witteveen, Naomi Baxter

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Cells process dynamic signaling inputs to regulate fate decisions during development. While oscillations or waves in key developmental pathways, such as Wnt, have been widely observed, the principles governing how cells decode these signals remain unclear. By leveraging optogenetic control of Wnt pathway both HEK293T and H9 human embryonic stem cells, we systematically map relationship between signal frequency downstream activation. We find that exhibit a minimal response at certain frequencies, behavior term anti-resonance. developed detailed biochemical simplified hidden variable models explain anti-resonance emerges from interplay fast slow dynamics. Remarkably, directly influences cell involved gastrulation; delivered anti-resonant frequencies result dramatically reduced mesoderm differentiation. Our work reveals previously unknown mechanism may filter against spurious These findings establish new insights into with implications for tissue engineering, regenerative medicine, cancer biology.

Language: Английский

Citations

0
Natural compounds as regulators of miRNAs: exploring a new avenue for treating brain cancer DOI
Ahmed S. Doghish, Walaa A. El‐Dakroury, Ahmed I. Abulsoud

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Language: Английский

Citations

0
A comparative analysis of planarian regeneration specificity reveals tissue polarity contributions of the axial cWnt signalling gradient DOI Open Access
James Cleland, Hanh Thi-Kim Vu, Johanna E. M. Dickmann

et al.

Published: March 13, 2025

Planarians exhibit remarkable whole-body regeneration abilities. The formation of heads at forward-facing wounds and tails rearward-facing suggests an intrinsic tissue polarity guiding regeneration. While the underlying mechanisms remain unclear, reports double-headed regenerates from increasingly narrow fragments have long been hypothesised to reflect gradient-based specification. Here, we systematically re-examine this hypothesis in modern model species Schmidtea mediterranea a representative genus likely used original studies, Girardia sinensis . never observed double-heads S. , G. readily regenerated manner dependent on piece length, anatomical position body size. We found that reduced robustness was partially explained by wound site-symmetric expression head determinant notum which is highly anterior-specific Exploring what else might mediate head/tail specificity examined role conserved tail-to-head cWnt signalling gradient. By developing time-resolved pharmacological approach reduce gradient slope without affecting wound-induced dynamics, increased incidence regenerates. In addition, size-dependence double-head correlated with decreasing steepness due scaling. Taken together, our results indicate may contribute planarian specificity. Furthermore, they suggest composed multiple parallely-acting cues, differential reliance contributes interspecies variation

Language: Английский

Citations

0
A comparative analysis of planarian regeneration specificity reveals tissue polarity contributions of the axial cWnt signalling gradient DOI Open Access
James Cleland, Hanh Thi-Kim Vu, Johanna E. M. Dickmann

et al.

Published: March 13, 2025

Planarians exhibit remarkable whole-body regeneration abilities. The formation of heads at forward-facing wounds and tails rearward-facing suggests an intrinsic tissue polarity guiding regeneration. While the underlying mechanisms remain unclear, reports double-headed regenerates from increasingly narrow fragments have long been hypothesised to reflect gradient-based specification. Here, we systematically re-examine this hypothesis in modern model species Schmidtea mediterranea a representative genus likely used original studies, Girardia sinensis . never observed double-heads S. , G. readily regenerated manner dependent on piece length, anatomical position body size. We found that reduced robustness was partially explained by wound site-symmetric expression head determinant notum which is highly anterior-specific Exploring what else might mediate head/tail specificity examined role conserved tail-to-head cWnt signalling gradient. By developing time-resolved pharmacological approach reduce gradient slope without affecting wound-induced dynamics, increased incidence regenerates. In addition, size-dependence double-head correlated with decreasing steepness due scaling. Taken together, our results indicate may contribute planarian specificity. Furthermore, they suggest composed multiple parallely-acting cues, differential reliance contributes interspecies variation

Language: Английский

Citations

0
The application of integrated bioinformatic tools to identify SRI, SMC2, PSIP1, TLE4, and MSX1 genes as potential markers in the diagnosis and therapy of osteoarthritis DOI
Jolanta Kryczka, Ewa Brzeziańska‐Lasota, Michał Pikuła

et al.

Published: May 9, 2025

Abstract Background: Osteoarthritis (OA) is the most common degenerative joint disease, leading to severe pain and functional disability for nearly 530 million people worldwide. OA characterized by progressive loss of cartilage synovial hyperplasia from articulating surfaces any diarthrodial joints, however, majority cases account hip knee. Currently, regenerative therapy based on stem cells has emerged as one promising rapidly evolving strategies in OA. Although progression potential regeneration can be monitored magnetic resonance imaging (MRI), we lack proper molecular markers diagnostic in vitro studies. Methods: Gene expression profiles articular (chondrocytes) synovium OA-affected patients’ were downloaded The Expression Omnibus database (GSE179716, GSE206848, GSE239343, GSE48556) analyzed using various bioinformatic tools platforms: GEO2R, FunRich, C-Big, Human Protein Atlas, STRING, Orange data mining, Jasp, Ontology Reactome. Results:OA-affected chondrocytes present differences between aurora B C signaling. However, major biological pathways are similarly enriched with SRI, SMC2, PSIP1, TLE4, MSX1 genes identified prominent biomarkers mesenchymal cell-based regeneration. Additionally, peripheral blood mononuclear (PBMCs) patients PSIP1 and TLE4 (respectively) down up-regulated mRNA levels. Conclusions:mRNA levels chosen indicate mainly vitro studies, whereas level ratio PSIP1:TLE4 PBMCs derived patients help monitor clinical practice.

Language: Английский

Citations

0
A comparative analysis of planarian regeneration specificity reveals tissue polarity contributions of the axial cWnt signalling gradient. DOI Creative Commons
James Cleland, Hanh Thi-Kim Vu, Johanna E. M. Dickmann

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Summary Planarians exhibit remarkable whole-body regeneration abilities. The formation of heads at forward-facing wounds and tails rearward-facing suggests an intrinsic tissue polarity guiding regeneration. While the underlying mechanisms remain unclear, reports double-headed regenerates from increasingly narrow fragments have long been hypothesised to reflect gradient-based specification. Here, we systematically re-examine this hypothesis in modern model species Schmidtea mediterranea a representative genus likely used original studies, Girardia sinensis . never observed double-heads S. , G. readily regenerated manner dependent on piece length, anatomical position body size. We found that reduced robustness was partially explained by wound site-symmetric expression head determinant notum which is highly anterior-specific Exploring what else might mediate head/tail specificity examined role conserved tail-to-head cWnt signalling gradient. By developing time-resolved pharmacological approach reduce gradient slope without affecting wound-induced dynamics, increased incidence regenerates. In addition, size-dependence double-head correlated with decreasing steepness due scaling. Taken together, our results indicate may contribute planarian specificity. Furthermore, they suggest composed multiple parallely-acting cues, differential reliance contributes interspecies variation

Language: Английский

Citations

0
Breaking Left–Right Symmetry by the Interplay of Planar Cell Polarity, Calcium Signaling and Cilia DOI Creative Commons

De‐Li Shi

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2116 - 2116

Published: Dec. 20, 2024

The formation of the embryonic left–right axis is a fundamental process in animals, which subsequently conditions both shape and correct positioning internal organs. During vertebrate early development, transient structure, known as organizer, breaks bilateral symmetry manner that critically dependent on activity motile immotile cilia or asymmetric cell migration. Extensive studies have partially elucidated molecular pathways initiate patterning morphogenesis. Wnt/planar polarity signaling plays an important role biased orientation rotational motion cilia. leftward fluid flow generated cavity organizer sensed by through complex mechanisms to trigger left-sided calcium lateralized gene expression pattern. Disrupted impaired structure function leads randomized determination, closely linked laterality defects, particularly congenital heart disease. Despite formidable progress made deciphering critical contribution establishing asymmetry, strong challenge remains understand how generate sense differentially activate across axis. This review analyzes underlying morphogenesis formation. It also aims identify questions are open for future investigations.

Language: Английский

Citations

0