Planar cell polarity is essential for the architectural patterning of the mammalian biliary tree DOI Creative Commons
Michaela Raab, Ersi Christodoulou, Roopesh Krishnankutty

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 20, 2023

Abstract In the developing liver, bipotent epithelial progenitor cells known as hepatoblasts undergo lineage segregation to form two major cell types, hepatocytes that constitute bulk of liver parenchyma and biliary (cholangiocytes) which comprise bile duct, a complex tubular network is critical for normal function. Notch TGFβ signalling promote formation sheet cells, ductal plate organises into discontinuous structures. How these structures elongate connect continuous duct remains undefined. Here, we show planar polarity protein, VANGL2 expressed late in intrahepatic development patterns cell-cell contacts between cells. The patterning regulates polarisation actin cytoskeleton within loss Vangl2 -function results abnormal distribution cortical remodelling resulting failure formation. Planar step post-specification sculpture essential establishing tissue architecture.

Язык: Английский

Advances of Wnt Signalling Pathway in Colorectal Cancer DOI Creative Commons

Yaoyao Zhu,

Xia Li

Cells, Год журнала: 2023, Номер 12(3), С. 447 - 447

Опубликована: Янв. 30, 2023

Colorectal cancer (CRC) represents one of the most common cancers worldwide, with a high mortality rate despite decreasing incidence and new diagnostic therapeutic strategies. CRC arises from both epidemiologic molecular backgrounds. In addition to hereditary factor genetic mutations, strongly varying is closely linked chronic inflammatory disorders intestine terrible dietary habits. The Wnt signalling pathway complex regulatory network that implicated in many physiological processes, including occurrence, development, prognosis, invasion, metastasis. It currently believed include classical Wnt/β-catenin, Wnt/PCP, Wnt/Ca2+. this review, we summarise recent mechanisms potential regulators three branches CRC.

Язык: Английский

Процитировано

56
The Helicobacter pylori CagA oncoprotein disrupts Wnt/PCP signaling and promotes hyperproliferation of pyloric gland base cells DOI
Atsushi Takahashi‐Kanemitsu, Mengxue Lu, Christopher T. G. Knight

и другие.

Science Signaling, Год журнала: 2023, Номер 16(794)

Опубликована: Июль 18, 2023

Helicobacter pylori strains that deliver the oncoprotein CagA into gastric epithelial cells are major etiologic agents of upper diseases including cancer. promotes carcinogenesis through interactions with multiple host proteins. Here, we show also disrupts Wnt-dependent planar cell polarity (Wnt/PCP), which orients within plane an epithelium and coordinates collective behaviors such as convergent extension to enable elongation during development. Ectopic expression in Xenopus laevis embryos impaired gastrulation, neural tube formation, axis elongation, processes driven by movements depend on Wnt/PCP pathway. Mice specifically expressing stomach had longer pyloric glands mislocalization tetraspanin proteins VANGL1 VANGL2 (VANGL1/2), critical components signaling. The increased gland length was due hyperproliferation at base, where Lgr5 + stem progenitor reside, associated fewer differentiated enteroendocrine cells. In cultured human cells, N terminus interacted C-terminal cytoplasmic tails VANGL1/2, signaling inducing VANGL1/2 from plasma membrane cytoplasm. Thus, may contribute development cancer subverting a Wnt/PCP-dependent mechanism restrains proliferation differentiation.

Язык: Английский

Процитировано

12
The role of prickle proteins in vertebrate development and pathology DOI Creative Commons
Katarzyna Anna Radaszkiewicz, Marie Šulcová,

E. Kohoutkova

и другие.

Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 479(5), С. 1199 - 1221

Опубликована: Июнь 26, 2023

Abstract Prickle is an evolutionarily conserved family of proteins exclusively associated with planar cell polarity (PCP) signalling. This signalling pathway provides directional and positional cues to eukaryotic cells along the plane epithelial sheet, orthogonal both apicobasal left–right axes. Through studies in fruit fly Drosophila , we have learned that PCP manifested by spatial segregation two protein complexes, namely Prickle/Vangl Frizzled/Dishevelled. While Vangl, Frizzled, Dishevelled been extensively studied, has largely neglected. likely because its role vertebrate development pathologies still being explored not yet fully understood. The current review aims address this gap summarizing our knowledge on cover their broad versatility. Accumulating evidence suggests involved many developmental events, contributes homeostasis, can cause diseases when expression properties are deregulated. highlights importance development, discusses implications Prickle-dependent pathology, points out blind spots or potential links regarding Prickle, which could be studied further.

Язык: Английский

Процитировано

11
Non-canonical WNT5A-ROR signaling: New perspectives on an ancient developmental pathway DOI
Sara E. Konopelski, Srisathya Srinivasan,

Courtney A. Dreyer

и другие.

Current topics in developmental biology/Current Topics in Developmental Biology, Год журнала: 2023, Номер unknown, С. 195 - 227

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

9
Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway DOI Creative Commons
Samar Ahmad, Tania Christova,

Melanie Pye

и другие.

Cells, Год журнала: 2025, Номер 14(1), С. 56 - 56

Опубликована: Янв. 6, 2025

In neurons, the acquisition of a polarized morphology is achieved upon outgrowth single axon from one several neurites. Small extracellular vesicles (sEVs), such as exosomes, diverse sources are known to promote neurite and thus may have therapeutic potential. However, effect fibroblast-derived exosomes on elongation in neurons central nervous system under growth-permissive conditions remains unclear. Here, we show that sEVs neuronal mouse primary embryonic cortical neurons. Mechanistically, demonstrate sEV-induced increase requires endogenous Wnts core PCP components including Prickle, Vangl, Frizzled, Dishevelled. We internalized by colocalize with Wnt7b, induce relocalization Vangl2 distal during outgrowth. contrast, derived or astrocytes do not outgrowth, while activated inhibit elongation. Thus, our data reveal through Wnt-PCP pathway manner dependent Wnts.

Язык: Английский

Процитировано

0
The bidirectional relationship between cilia and PCP signaling pathway core protein Vangl2 DOI Creative Commons

Huanyong Qin,

Ting Liang,

Chuanfen Zhang

и другие.

Science Progress, Год журнала: 2025, Номер 108(1)

Опубликована: Янв. 1, 2025

Vangl2, a core component of the PCP signaling pathway, serves as scaffold protein on cell membrane, playing crucial role in organizing complexes. Cilia, dynamic structures surface, carry out wide range functions. Research has highlighted bidirectional regulatory interaction between Vangl2 and cilia, underscoring their interconnected roles cellular processes. This relationship is demonstrated by localization at base proximal regions where it plays essential ciliary positioning, asymmetric distribution, ciliogenesis. In contrast, absence cilia can disrupt Vangl2-mediated signal transduction review offers narrative recent research Vangl2's function examines effects signaling.

Язык: Английский

Процитировано

0
Bud, Branch, Breathe! Building a mammalian lung over space and time DOI Creative Commons
Brigid L.M. Hogan

Developmental Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Many mammalian organs, such as the mammary and lachrymal glands, kidney lungs develop by process known branching morphogenesis. An essential feature of this is reciprocal interaction between inner branched tubular epithelium surrounding mesenchyme to optimize final amount epithelial tissue that generated for specific functions. To achieve expansion initial population undergoes repeated rounds bud formation, branch outgrowth tip bifurcations, with each repertoire requiring dynamic changes in cell behavior. The morphogenesis was first studied experimentally Grobstein others who showed embryonic did not without so-called inductive signals from mesenchyme. However, it whether activity uniformly distributed throughout mesoderm or localized regions. mouse lung seen a powerful system which investigate questions since its early highly stereotypic, both vivo culture. This advantage exploited two young scientists, Alescio Cassini, used grafting techniques explanted lungs. They around distal buds could induce ectopic trachea other non-branching regions epithelium. At same time, denuded their failed further. speculated factors promote formation continued competent endoderm are specifically within mesenchyme, establishing conceptual framework future experimentation. Since then, advances many areas biology bioengineering have enabled identification gene regulatory networks, signaling pathways biomechanical properties mediate quantitative model how these parameters coordinated over space time control pattern scale overall size lung, still remains elusive.

Язык: Английский

Процитировано

0
Interacting Fat1 and Dchs Planar Cell Polarity Proteins Supported by Fjx1 Serve as Heterodimeric Intercellular Bridges Crucial to Support Spermatogenesis DOI

Tiao Bu,

Lingling Wang, Xiaolong Wu

и другие.

Advances in experimental medicine and biology, Год журнала: 2025, Номер unknown, С. 355 - 374

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Frizzled receptors: gatekeepers of Wnt signaling in development and disease DOI Creative Commons
Dalia Martinez‐Marin,

Grace C. Stroman,

Camryn J. Fulton

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Май 1, 2025

Frizzled (FZD) receptors are a subset of G-protein-coupled (GPCRs), the largest class human cell surface and major target FDA-approved drugs. Activated by Wnt ligands, FZDs regulate key cellular processes such as proliferation, differentiation, polarity, positioning them at intersection developmental biology disease, including cancer. Despite their significance, FZD signaling remains incompletely understood, particularly in distinguishing receptor-specific roles across canonical non-canonical pathways. Challenges include defining ligand-receptor specificity, elucidating signal transduction mechanisms, understanding influence post translational modifications context. Structural dynamics, receptor trafficking, contributions also remain areas active investigation. Recent advances structural biology, transcriptomics, functional genomics beginning to address these gaps, while emerging therapeutic approaches-such small-molecule modulators antibodies-highlight potential drug targets. This review synthesizes current insights into examines ongoing controversies, outlines promising directions for future research development.

Язык: Английский

Процитировано

0
Van Gogh-like 2 is essential for the architectural patterning of the mammalian biliary tree DOI Creative Commons
Michaela Raab, Ersi Christodoulou, Roopesh Krishnankutty

и другие.

Journal of Hepatology, Год журнала: 2024, Номер 81(1), С. 108 - 119

Опубликована: Март 7, 2024

In the developing liver, bipotent epithelial progenitor cells undergo lineage segregation to form hepatocytes, which constitute bulk of liver parenchyma, and biliary (cholangiocytes), comprise bile duct (a complex tubular network that is critical for normal function). Notch TGFβ signalling promote formation a sheet cells, ductal plate, organises into discontinuous structures. How these structures elongate connect continuous remains undefined. We aimed define mechanisms by plate transitions from simple connected duct.

Язык: Английский

Процитировано

2