Article
Biochemistry & Molecular Biology
Fei Fang, McKenzie Sup, Andrew Luzzi, Xavier Ferrer, Stavros Thomopoulos
Summary: Hh signaling plays essential roles in the development and repair of tendons and entheses, but its overactivation can lead to pathological ossification. Further research is needed to understand its distinct functions in tendons and entheses.
Article
Oncology
Daosen Chen, Xiaodiao Kang, Zhenxing Li, Liang Chen, Qiong Ma, Pei Fan
Summary: The study investigated the role of Hedgehog/GLI1 signaling pathway in regulating cisplatin resistance in osteosarcoma. Results showed that GLI1 was up-regulated in OS patients and cisplatin-resistant cells. Silencing GLI1 restored sensitivity to cisplatin and inhibited proliferation, migration, and colony formation, while increasing apoptosis. Furthermore, using a Hedgehog pathway inhibitor GANT61 in xenograft model demonstrated inhibition of tumor growth.
Review
Cell Biology
Dian Jing, Chaoyuan Li, Ke Yao, Xudong Xie, Peiqi Wang, Hu Zhao, Jian Q. Feng, Zhihe Zhao, Yafei Wu, Jun Wang
Summary: Gli1(+) MSCs, as a type of crucial mesenchymal stem cells, are responsible for various tissue developments, homeostasis, and injury repair. They play critical roles in the development and homeostasis of a variety of hard and soft tissues.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Oncology
Anke Koeniger, Anna Brichkina, Iris Nee, Lukas Dempwolff, Anna Hupfer, Ilya Galperin, Florian Finkernagel, Andrea Nist, Thorsten Stiewe, Till Adhikary, Wibke Diederich, Matthias Lauth
Summary: Elevated GLI1 expression levels are associated with improved survival in NB patients and GLI1 overexpression exerts tumor-suppressive traits in cultured NB cells. However, NB cells are protected from increased GLI1 levels as they have lost their primary cilia and ability to transduce Hedgehog signals. An isoxazole molecule (ISX) has been identified to activate GLI1 independently of primary cilia, providing a potential therapeutic strategy for NB treatment.
Article
Biochemistry & Molecular Biology
Wei Wang, Taiqiang Yan, Wei Guo, Jianfang Niu, Zhiqing Zhao, Kunkun Sun, Hongliang Zhang, Yiyang Yu, Tingting Ren
Summary: The study identified a novel mechanism regulating HH-independent GLI1 expression in chondrosarcoma, involving the MVP protein and the mTOR/S6K1 signaling cascade. Inhibition of MVP and GLI1 together strongly suppressed tumor growth in vitro and in vivo. This finding provides a rationale for combination therapy in advanced chondrosarcoma patients.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Raphael Luis Rocha Nogueira, Tais Bacelar Sacramento de Araujo, Ludmila Faro Valverde, Viviane Aline Oliveira Silva, Bruno Raphael Ribeiro Cavalcante, Erik Aranha Rossi, Kyan James Allahdadi, Mitermayer Galvao dos Reis, Thiago Almeida Pereira, Ricardo D. Coletta, Daniel Pereira Bezerra, Bruno Solano de Freitas Souza, Rosane Borges Dias, Clarissa A. Gurgel Rocha
Summary: The present study evaluated the therapeutic potential of Arsenic Trioxide (ATO) in treating Oral Squamous Cell Carcinoma (OSCC). The results showed that ATO has antitumoral effects and inhibits the Hedgehog (HH) pathway. Furthermore, ATO also induced changes in cell morphology and cell cycle in oral cancer cells.
Article
Plant Sciences
Mengjie Li, Tingting Guo, Jiayi Lin, Xia Huang, Qiaodan Ke, Yujian Wu, Chunping Fang, Chenxia Hu
Summary: Curcumin, the main pharmacological component extracted from Curcuma longa L, has been found to inhibit proliferation and metastasis of TNBC cells via the Hedgehog/Gli1 pathway, providing potential therapeutic strategies for TNBC.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Cell Biology
Weiyi Gong, Wenxuan Zhao, Gang Liu, Lei Shi, Xia Zhao
Summary: BDDD-721, a curcumin analogue, exhibits stronger anti-tumor activity than curcumin on medulloblastoma. It effectively inhibits the proliferation, migration, invasion, and promotes apoptosis of medulloblastoma cells. The study also discovered that BDDD-721 targets the Shh/Gli1 signaling pathway to exert its anticancer effects.
Article
Plant Sciences
Shi-Hao Ni, Xiao-Jiao Zhang, Xiao-Lu OuYang, Tao-Chun Ye, Jin Li, Yue Li, Shu-Ning Sun, Xiao-Wei Han, Wen-Jie Long, Ling-Jun Wang, Zhong-Qi Yang, Lu Lu
Summary: This study demonstrates that long-term kidney damage and dialysis may lead to muscle wasting and ferroptosis, and Lobetyolin (LBT) may alleviate muscle injury by inhibiting ferroptosis through activation of the Hedgehog signaling pathway.
Article
Biochemistry & Molecular Biology
Xiaofeng Zhou, Yingting He, Xiangchun Pan, Hongyan Quan, Bo He, Yongguang Li, Guofeng Bai, Nian Li, Zhe Zhang, Hao Zhang, Jiaqi Li, Xiaolong Yuan
Summary: DNA methylation and lncRNAs play important roles in follicular development. However, the mechanisms of lncRNAs mediated by DNA methylation in follicular development are still unclear. In this study, we found that inhibiting DNMT1 expression promotes granulosa cell apoptosis and inhibits follicular development. We identified a novel lncRNA called IFFD that is regulated by DNMT1 and inhibits follicular development by affecting granulosa cell proliferation, estrogen secretion, and apoptosis.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell & Tissue Engineering
Rupali Lav, Jan Krivanek, Neal Anthwal, Abigail S. Tucker
Summary: In the murine molar, Wnt signals from Gli1+ stem/progenitor cells play a crucial role in coordinating root development and regulating interactions between mesenchymal and epithelial cells via the SOX9 pathway. Loss of Wnt production in Gli1+ cells leads to mis-regulation of key signaling pathways, resulting in truncation of root development and loss of epithelial identity. Stabilization of Wnt signaling in the apical papilla causes rapid differentiation of hard tissues and fragmentation of the epithelial root sheath.
Article
Developmental Biology
Adam W. Olson, Vien Le, Jinhui Wang, Alex Hiroto, Won Kyung Kim, Dong-Hoon Lee, Joseph Aldahl, Xiwei Wu, Minhyung Kim, Gerald R. Cunha, Sungyong You, Zijie Sun
Summary: The study demonstrates that stromal androgen receptor (AR) action is crucial for prostate development, and selective deletion of stromal AR expression in prepubescent Gli1-expressing cells disrupts androgen signaling-initiated stromal-epithelial paracrine interactions, leading to growth retardation and developmental defects in pubertal prostate epithelia. Aberrant shh-signaling activation and altered differentiation fates of prostatic epithelial cells are identified as key mechanisms affected by stromal AR deletion.
Article
Cardiac & Cardiovascular Systems
Rui Peng, Binbin Li, Shuxia Chen, Zhiwen Shi, Liwei Yu, Yunqian Gao, Xueyan Yang, Lei Lu, Hongyan Wang
Summary: This study identified mutations in GLI1-3 genes that are associated with congenital heart disease (CHD), affecting the balance of the Sonic hedgehog (SHH) signaling pathway and providing new insights into the genetic mechanism of embryo cardiogenesis regulated by SHH signaling.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Mingwei Sheng, Yuanbang Lin, Dongwei Xu, Yizhu Tian, Yongqiang Zhan, Changyong Li, Douglas G. Farmer, Jerzy W. Kupiec-Weglinski, Bibo Ke
Summary: The CD47-SIRP alpha signaling pathway plays a crucial role in MSC-mediated immune regulation during sterile inflammatory liver injury. Activation of this pathway controls NEK7/NLRP3 activity through a direct interaction between Gli1 and NICD, which modulates the inflammatory response in MSC-immunotherapy.
Article
Multidisciplinary Sciences
Elle C. Roberson, Ngan Kim Tran, Anushka N. Godambe, Harrison Mark, Michelle Nguimtsop, Trinity Rust, Elizabeth Ung, LeCaine J. Barker, Rebecca D. Fitch, John B. Wallingford
Summary: Decades of research have shown that the mammalian estrous cycle is regulated by cycling steroid hormones. However, the signaling mechanisms connecting hormonal action and the physical changes in the uterus during the cycle are still unclear. In this study, gene expression during all stages of the mouse estrous cycle was analyzed, revealing that several genetic programs responsible for tissue morphogenesis in developing embryos display cyclical patterns of expression. Furthermore, it was found that most of the genes involved in the Hedgehog signaling pathway are transcribed cyclically in the uterus. Disruption of the Hedgehog receptor smoothened not only affects the normal thickening of the endometrial lining but also induces abnormal deformation of the uterine smooth muscle. These findings provide insights into the mechanisms underlying normal uterine remodeling and cyclical gene expression.
Article
Biochemistry & Molecular Biology
Dirk Hubmacher, Nandaraj Taye, Zerina Balic, Stetson Thacker, Sheila M. Adams, David E. Birk, Ronen Schweitzer, Suneel S. Apte
Article
Developmental Biology
Shai Eyal, Shiri Kult, Sarah Rubin, Sharon Krief, Neta Felsenthal, Kyriel M. Pineault, Dena Leshkowitz, Tomer-Meir Salame, Yoseph Addadi, Deneen M. Wellik, Elazar Zelzer
Article
Biology
Guak-Kim Tan, Brian A. Pryce, Anna Stabio, John V. Brigande, ChaoJie Wang, Zheng Xia, Sara F. Tufa, Douglas R. Keene, Ronen Schweitzer
Article
Biochemical Research Methods
Tomer Stern, Stanislav Y. Shvartsman, Eric F. Wieschaus
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Developmental Biology
Saundra Y. Schlesinger, Seongkyung Seo, Brian A. Pryce, Sara F. Tufa, Douglas R. Keene, Alice H. Huang, Ronen Schweitzer
Summary: This study established a novel murine model of joint contracture by targeting Smad4 deletion in the tendon cell lineage. Smad4(ScxCre) mutants showed joint contracture shortly after birth, with severity increasing with age. Disruption of the BMP pathway in Alk3(ScxCre)/Alk6(null) mutants replicated many features of the joint contracture phenotype, suggesting a role for BMP signaling in tendon elongation and extracellular matrix accumulation.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Rocky Diegmiller, Caroline A. Doherty, Tomer Stern, Jasmin Imran Alsous, Stanislav Y. Shvartsman
Summary: Size is a fundamental feature in living organisms, linked to their function. Though scaling laws have been a powerful tool for studying growth dynamics, especially in single cells, the coordinated growth of multicellular structures still faces technical challenges. This study presents a supervised learning approach for quantifying growth dynamics in germline cysts, revealing patterns induced by developmental dynamics and differential growth rates of organelles. Leveraging imaging data, this approach can be applied to studying collective cell growth in various developmental contexts.
Article
Multidisciplinary Sciences
Joohyun Lim, Caressa Lietman, Matthew W. Grol, Alexis Castellon, Brian Dawson, Mary Adeyeye, Jyoti Rai, MaryAnn Weis, Douglas R. Keene, Ronen Schweitzer, Dongsu Park, David R. Eyre, Deborah Krakow, Brendan H. Lee
Summary: This study reveals that defects in Fkbp10 in tendons and ligaments can cause joint dysfunction in osteogenesis imperfecta, involving ectopic chondrogenesis and dysregulated Hedgehog signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Sarah Rubin, Ankit Agrawal, Johannes Stegmaier, Sharon Krief, Neta Felsenthal, Jonathan Svorai, Yoseph Addadi, Paul Villoutreix, Tomer Stern, Elazar Zelzer
Summary: The 3D MAPs pipeline allows for the characterization of morphogenetic behaviors of chondrocytes while retaining spatial context, aiding in the study of bone development. The analysis revealed a wide range of morphological changes, growth strategies, and cell organizations in bones, as well as abnormalities in Gdf5 KO tibias, providing insights into cellular mechanisms regulating the differentiation process.
NATURE COMMUNICATIONS
(2021)
Article
Physics, Multidisciplinary
Matej Krajnc, Tomer Stern, Clement Zankoc
Summary: Active cell-junction remodeling is crucial for tissue morphogenesis, with instability triggering cell intercalations. A mechanical model describing junctions as dynamic active force dipoles reveals nonlinearities in tissue's elastic response stabilizing collapse through limit cycles or condensation of junction lengths. Additionally, active junction networks undergo collective instability, driving in-plane ordering or developing a limit cycle of oscillations extending over distinct network topologies in the energy landscape.
PHYSICAL REVIEW LETTERS
(2021)
Article
Cell & Tissue Engineering
Guak-Kim Tan, Brian A. Pryce, Anna Stabio, Douglas R. Keene, Sara F. Tufa, Ronen Schweitzer
Summary: This study reveals that in damaged tendons, stem/progenitor cells are recruited directly into the tissue, originating from a Sox9-expressing lineage and their recruitment being dependent on cell autonomous TGF beta signaling. This recruitment differs from previous reports and highlights the critical role of TGF beta signaling in cell recruitment for tendon repair.
Article
Pathology
Ron C. Vinestock, Neta Felsenthal, Eran Assaraf, Eldad Katz, Sarah Rubin, Lia Heinemann-Yerushalmi, Sharon Krief, Nili Dezorella, Smadar Levin-Zaidman, Michael Tsoory, Stavros Thomopoulos, Elazar Zelzer
Summary: This study reveals a unique healing mechanism in neonatal entheses, where local extracellular matrix secretion by resident cells forms an acellular deposit without inflammation, allowing gait restoration. Understanding the healing mechanism of this complex transitional tissue may lead to new therapeutic strategies for adult enthesis injuries.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tomer Stern, Stanislav Y. Shvartsman, Eric F. Wieschaus
Summary: Gastrulation movements in animal embryos are driven by regulated deformations of patterned epithelial sheets, and understanding the cellular processes and large-scale tissue deformations involved is crucial for studying animal development. Recent advances in microscopy and image processing provide a unique opportunity to integrate these complementary viewpoints, allowing for a better understanding of the early stages of gastrulation. By utilizing a computational framework for cell segmentation and tracking, as well as efficient algorithms for event detection, this study provides insights into the cellular activity patterns and quantitative relations between intercalation frequency and axis elongation during early Drosophila embryo gastrulation.
Article
Cell Biology
Neta Felsenthal, Danijela Matic Vignjevic
Summary: The epithelium of the small intestine consists of crypts and villi, with intrinsic cell behaviors and coordination between epithelium and fibroblasts playing crucial roles in tissue morphogenesis and gene expression.
CURRENT OPINION IN CELL BIOLOGY
(2022)