Article
Developmental Biology
Yanshu Wang, Arjun Venkatesh, Jiajia Xu, Mingxin Xu, John Williams, Philip M. Smallwood, Aaron James, Jeremy Nathans
Summary: In vascular endothelial cells of the central nervous system, signaling involving ligands WNT7A and WNT7B and co-activator proteins GPR124 and RECK is crucial for limb development. Reductions in the function of these ligands and/or co-activators result in decreased and abnormal limb bone growth, as well as other limb phenotypes. These findings demonstrate that the WNT7A/WNT7B-FRIZZLED-LRP5/LRP6-GPR124-RECK signaling system functions as a unified unit in limb development.
Article
Oncology
Courtney A. Dreyer, Kacey VanderVorst, Dean Natwick, George Bell, Prachi Sood, Maria Hernandez, James M. Angelastro, Sean R. Collins, Kermit L. Carraway III
Summary: In this study, we found that the non-canonical Wnt planar cell polarity (Wnt/PCP) signaling pathway components Vangl1 and Fzd7 promote the malignancy of glioblastoma multiforme (GBM) by enhancing cellular proliferation, migration, and invasiveness. They also activate Rho GTPases to regulate cytoskeletal rearrangements and actin dynamics in migrating GBM cells. We discovered a novel Vangl1/Fzd7 complex at the leading edge of migratory GBM cells, which is critical for recruiting downstream effectors to promote tumor progression. Depletion of FZD7 resulted in suppressed tumor growth, delayed latency, and improved overall survival in a mouse xenograft model, suggesting that targeting the Wnt/PCP pathway could be a potential therapeutic strategy for GBM patients.
Article
Cell Biology
Andre Landin Malt, Shaylyn Clancy, Diane Hwang, Alice Liu, Connor Smith, Margaret Smith, Maya Hatley, Christopher Clemens, Xiaowei Lu
Summary: A non-canonical Wnt signaling pathway has been found to promote cochlear outgrowth and coordinate planar polarization of hair cells. Gsk3 beta and Rac1 play crucial roles in this pathway, as shown in genetic rescue experiments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Hyun-Taek Kim, Paolo Panza, Khrievono Kikhi, Yuko Nakamichi, Ann Atzberger, Stefan Guenther, Clemens Ruppert, Andreas Guenther, Didier Y. R. Stainier
Summary: This study reveals that WNT/RYK signaling plays a regulatory role in lung diseases and highlights the anti-inflammatory modulation of RYK signaling in lung development and homeostasis. These findings provide an animal model for further investigation of the etiology and therapeutic approaches to inflammatory lung diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yeon Sun Kim, Yingju Li, Jia Yuan, Jean-Paul Borg, Xiaofei Sun, Sudhansu K. Dey
Summary: Directed trophoblast migration towards the maternal mesometrial pole is crucial for successful placentation and pregnancy. Deficiencies in trophoblast invasion can result in various pregnancy complications. The interaction between VANGL2 and CB1 plays a critical role in trophoblast invasion and movement regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Kacey VanderVorst, Courtney A. Dreyer, Jason Hatakeyama, George R. R. Bell, Julie A. Learn, Anastasia L. Berg, Maria Hernandez, Hyun Lee, Sean R. Collins, Kermit L. Carraway III
Summary: The study examines the role of Wnt/planar cell polarity (Wnt/PCP) signaling pathway in breast tumor cell motility, collective cell invasiveness, and mammary tumor metastasis. The findings demonstrate that Vangl-dependent Wnt/PCP signaling promotes breast cancer collective cell migration and facilitates distant metastasis.
BREAST CANCER RESEARCH
(2023)
Article
Developmental Biology
Sayuki Hirano, Yusuke Mii, Guillaume Charras, Tatsuo Michiue
Summary: This study reveals how mechanical signals regulate planar cell polarity (PCP) in the posterior neuroectoderm of Xenopus laevis. It shows that tension in the anterior-posterior direction plays a crucial role in maintaining PCP, and that cells sense tissue stretch indirectly through changes in their shape. Furthermore, the study suggests a cooperative relationship between tissue stretch direction and the diffusion of locally expressed Wnt ligands in establishing PCP.
Article
Medicine, Research & Experimental
Lili Zhu, Xiaobei Yang, Jingyu Feng, Jian Mao, Qidong Zhang, Mengru He, Yang Mi, Yingwu Mei, Ge Jin, Haifeng Zhang
Summary: The study reveals that CYP2E1 plays a role in hepatocarcinogenesis by manipulating the Wnt/Dvl2/beta-catenin pathway through inducing ROS accumulation, which leads to the inhibition of tumor growth and metastasis.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Cell Biology
Courtney A. Dreyer, Kacey VanderVorst, Kermit L. Carraway
Summary: This article discusses the importance of Wnt/planar cell polarity (Wnt/PCP) signaling in the establishment of polarity and cellular motility events in developing and adult tissues. It highlights the role of the transmembrane protein Vangl as a master scaffold for Wnt/PCP signaling and explores how dysregulation of these processes contributes to human diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
De-Li Shi
Summary: Gastrulation and neurulation are crucial morphogenetic processes involving cellular and molecular mechanisms to shape the embryonic body plan. Planar cell polarity proteins play a significant role in regulating these processes and their mutation can lead to various developmental defects and congenital diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Muhammad S. Alam, Shizuka Otsuka, Nathan Wong, Aamna Abbasi, Matthias M. Gaida, Yu Fan, Daoud Meerzaman, Jonathan D. Ashwell
Summary: The study revealed that TNF can induce the differentiation of mouse CD4(+) T cells into proinflammatory Th17 cells, mediated by the nondeath TNF receptor TNFR2, and also has an impact on the generation of proinflammatory Th1 cells. Additionally, TNFR2-deficient CD4(+) T cells showed lower pathogenicity in EAE and colitis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Lauren V. Albrecht, Nydia Tejeda-Munoz, Edward M. De Robertis
Summary: Recent investigations have revealed that Wnt signaling can regulate various cell physiological effects, promoting cell growth by mechanisms such as Wnt receptor endocytosis, Wnt-induced protein stabilization, and metabolic changes. A key element is the sequestration of glycogen synthase kinase 3 (GSK3) inside multivesicular bodies and lysosomes, which affects the phosphorylation motifs of GSK3 and protein degradation. These effects are independent of new protein synthesis and contribute to cell growth.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 37
(2021)
Article
Oncology
Zizhan Li, Shuangshuang Wang, Songling Fang, Xin Li, Yaohua Li, Gangli Liu
Summary: In this study, it was found that ADSCs can promote the occurrence and development of OSCC by activating the Wnt/PCP signaling pathway. The expression of proteins CTHRC1 and p-c-Jun significantly increased with enhanced interaction between ADSCs and OSCC cells. These findings contribute to a better understanding of the pathogenesis of OSCC and provide potential therapeutic targets for further research.
TRANSLATIONAL CANCER RESEARCH
(2022)
Review
Chemistry, Medicinal
Michelle F. Griffin, Julika Huber, Fahy J. Evan, Natalina Quarto, Michael T. Longaker
Summary: Skin fibrosis refers to the excessive deposition of extracellular matrix in the dermis, often leading to scar formation following tissue injury. The Wnt signaling pathways play a critical role in regulating skin scarring and interact with other fibrotic molecular pathways to cause skin fibrosis. Understanding the role of Wnt pathway in cutaneous fibrosis is essential for accelerating the development of effective Wnt modulators for the treatment of skin fibrosis.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Medicine, Research & Experimental
Lingling Kong, Yang Yu, Hui Guan, Liyang Jiang, Fenghao Sun, Xiaolin Li, Wei Huang, Baosheng Li
Summary: TGIF1 is highly expressed in esophageal cancer and plays an oncogenic role by promoting proliferation, migration, and invasion of cancer cells. It may achieve this by regulating the Wnt/β-catenin and Akt/mTOR signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Kinga Duszyc, Guillermo A. Gomez, Anne K. Lagendijk, Mei-Kwan Yau, Bageshri Naimish Nanavati, Briony L. Gliddon, Thomas E. Hall, Suzie Verma, Benjamin M. Hogan, Stuart M. Pitson, David P. Fairlie, Robert G. Parton, Alpha S. Yap
Summary: Extrusion is the primary response to apoptosis in epithelial cells, involving E-cadherin and RhoA signaling pathways. Mechanical tension-sensitive mechanotransduction activates RhoA specifically in neighboring cells of apoptotic cells, with S1P also playing a crucial role in the process.
Article
Multidisciplinary Sciences
Charlotte D. Koopman, Jessica De Angelis, Swati P. Iyer, Arie O. Verkerk, Jason Da Silva, Geza Berecki, Angela Jeanes, Gregory J. Baillie, Scott Paterson, Veronica Uribe, Ophelia Ehrlich, Samuel D. Robinson, Laurence Garric, Steven Petrou, Cas Simons, Irina Vetter, Benjamin M. Hogan, Teun P. de Boer, Jeroen Bakkers, Kelly A. Smith
Summary: Tmem161b has been identified as a highly conserved regulator of cardiac rhythm in zebrafish and mice, functioning to modulate ion channel activity. Loss of function in Tmem161b leads to cardiac arrhythmia and it is implicated as a candidate gene in heritable cardiac arrhythmia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Kazuhide S. Okuda, Mikaela Keyser, David B. Gurevich, Caterina Sturtzel, Elizabeth A. Mason, Scott Patterson, Huijun Chen, Mark Scott, Nicholas D. Condon, Paul Martin, Martin Distel, Benjamin M. Hogan
Summary: Angiogenesis is regulated by VEGF signaling pathways, with Erk playing a central role as a downstream effector. This study demonstrates the real-time imaging of Erk signaling dynamics in angiogenesis using a vascular Erk biosensor transgenic line in zebrafish. It reveals a dynamic sequence of Erk signaling events in regenerative angiogenesis, providing a new resource for studying vascular Erk signaling in real-time.
Article
Anatomy & Morphology
Tevin C. Y. Chau, Sungmin Baek, Baptiste Coxam, Renae Skoczylas, Maria Rondon-Galeano, Neil I. Bower, Elanor N. Wainwright, Steven A. Stacker, Helen M. Cooper, Peter A. Koopman, Anne K. Lagendijk, Natasha L. Harvey, Mathias Francois, Benjamin M. Hogan
Summary: Lymphatic vascular development is regulated by signaling and transcriptional pathways, including canonical and non-canonical WNT signaling. The interaction between Pkd1 and the non-canonical WNT signaling pathway controls LEC polarity and the morphogenesis of developing vessel networks through mutually suppressive roles. The findings suggest that Pkd1 acts by regulating non-canonical WNT signaling during the formation of lymphatic vascular networks.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Cell Biology
Abdulsalam I. Isiaku, Zuobing Zhang, Vahid Pazhakh, Harriet R. Manley, Ella R. Thompson, Lucy C. Fox, Satwica Yerneni, Piers Blombery, Graham J. Lieschke
Summary: The study introduced transgenic lines allowing for the distinction of phagocyte function in zebrafish, demonstrating the individual contributions of neutrophil- and macrophage-expressed genes to various physiological processes and diseases. Efficient gene editing was achieved in both neutrophils and macrophages, providing improved tools for research in zebrafish models.
DISEASE MODELS & MECHANISMS
(2021)
Article
Biology
Hannah M. Isles, Catherine A. Loynes, Sultan Alasmari, Fu Chuen Kon, Katherine M. Henry, Anastasia Kadochnikova, Jack Hales, Clare F. Muir, Maria-Cristina Keightley, Visakan Kadirkamanathan, Noemie Hamilton, Graham J. Lieschke, Stephen A. Renshaw, Philip M. Elks
Summary: Neutrophils are rapidly recruited to inflammatory sites where they form clusters through a process called neutrophil swarming. Study using transgenic zebrafish larvae shows that neutrophil swarming is a conserved process in zebrafish immunity and involves the release of cellular components by pioneer neutrophils to initiate the swarming process.
Article
Chemistry, Medicinal
Kazuhide S. Okuda, Mei Fong Ng, Nur Faizah Ruslan, Neil Bower, Dedrick Soon Seng Song, Huijun Chen, Sungmin Baek, Philip S. Crosier, Katarzyna Koltowska, Jonathan W. Astin, Pei Jean Tan, Benjamin M. Hogan, Vyomesh Patel
Summary: Lymphangiogenesis plays critical roles in disease, and studies have shown that CDF can effectively inhibit lymphangiogenesis by interfering with the VEGFC-VEGFR3-ERK signaling pathway. These findings suggest that CDF may be a candidate for treating metastasis and diseases of aberrant lymphangiogenesis.
Article
Multidisciplinary Sciences
Jennifer A. E. Payne, Julien Tailhades, Felix Ellett, Xenia Kostoulias, Alex J. Fulcher, Ting Fu, Ryan Leung, Stephanie Louch, Amy Tran, Severin A. Weber, Ralf B. Schittenhelm, Graham J. Lieschke, Chengxue Helena Qin, Daniel Irima, Anton Y. Peleg, Max J. Cryle
Summary: Researchers linked formylated peptides, which act as chemoattractants for neutrophils, with the antibiotic vancomycin, and found that these hybrid compounds improve the clearance of S. aureus by neutrophils.
NATURE COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Sahar Sadat Mahshid, Aliaa Monir Higazi, Jacqueline Michelle Ogier, Alain Dabdoub
Summary: Rapid diagnostic testing is essential in patient care, but there is currently no rapid diagnostic test for hearing loss. Researchers are exploring potential biomarkers for inner ear-related disorders and advancements in biosensor technology to enable accurate diagnostics and personalized therapy in the future. These biomarkers could provide valuable information on the site of damage in the inner ear, aiding in treatment assessment.
Article
Genetics & Heredity
Jacqueline M. Ogier, Yujing Gao, Eileen M. Dunne, Michael A. Wilson, Sarath C. Ranganathan, Gregory H. Tesch, David JNikolic Paterson, Alain Dabdoub, Rachel A. Burt, Bryony A. Nayagam, Paul J. Lockhart
Summary: Aminoglycoside antibiotics can cause toxic effects on the sensory hair cells in the inner ear, leading to permanent hearing loss and vestibular impairment. This study investigates the potential of ASK1 inhibition as a novel strategy to prevent aminoglycoside ototoxicity, providing significant pre-clinical evidence.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Correction
Genetics & Heredity
Jacqueline M. Ogier, Yujing Gao, Eileen M. Dunne, Michael A. Wilson, Sarath C. Ranganathan, Gregory H. Tesch, David J. Nikolic Paterson, Alain Dabdoub, Rachel A. Burt, Bryony A. Nayagam, Paul J. Lockhart
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Developmental Biology
Tevin C. Y. Chau, Mikaela S. Keyser, Jason A. Da Silva, Elysse K. Morris, Teodor E. Yordanov, Kinga P. Duscyz, Scott Paterson, Alpha S. Yap, Benjamin M. Hogan, Anne Karine Lagendijk
Summary: This study reveals the critical role of integrin adaptor protein in vascular morphogenesis, highlighting its key functions in EC elongation and junction linearisation. It also points out the significance of FAs in regulating cell morphology and vascular permeability.
Article
Biology
Yunpei Zhang, Lingling Neng, Kushal Sharma, Zhiqiang Hou, Anatasiya Johnson, Junha Song, Alain Dabdoub, Xiaorui Shi
Summary: The inner ear relies on pericytes to maintain the health of sensory hair cells and normal hearing. However, the specific contributions of pericytes to the auditory vascular-neuronal complex in the spiral ganglion are not fully understood. This study used a pericyte depletion mouse model to show that the loss of pericytes leads to vascular volume and spiral ganglion neuron loss, resulting in negatively impacted hearing sensitivity. Through in vitro experiments, it was discovered that pericytes promote the growth of neurites and vascular branches in neonatal and adult spiral ganglion explants, with this neural growth being mediated by pericyte-released exosomes containing vascular endothelial growth factor-A (VEGF-A).
Article
Biology
Kimberly J. Morgan, Karen Doggett, Fansuo Geng, Stephen Mieruszynski, Lachlan Whitehead, Kelly A. Smith, Benjamin M. Hogan, Cas Simons, Gregory J. Baillie, Ramyar Molania, Anthony T. Papenfuss, Thomas E. Hall, Elke A. Ober, Didier Y. R. Stainier, Zhiyuan Gong, Joan K. Heath
Summary: Reducing ahctf1 gene dosage significantly decreases liver volume in a hepatocellular carcinoma model and impairs nuclear pore formation, mitotic spindle assembly, and chromosome segregation in the context of cancer, leading to DNA damage and cell death.
Article
Hematology
Huimin Cao, Shalin H. Naik, Daniela Amann-Zalcenstein, Peter Hickey, Agus Salim, Benjamin Cao, Susan K. Nilsson, M. Cristina Keightley, Graham J. Lieschke
Summary: This study identifies the crucial role of the ZBTB11 transcription factor in definitive hematopoiesis. Deletion of ZBTB11 in mice leads to embryonic death and hematopoietic failure. Loss of ZBTB11 results in overspecification of hematopoietic stem cells, loss of stemness, impaired differentiation, and cell cycle regulation. This study highlights the cell-intrinsic requirement of ZBTB11 in maintaining a pool of maturation-capable HSCs and progenitor cells.