Article
Pharmacology & Pharmacy
Alex Pezzotta, Ilaria Gentile, Donatella Genovese, Maria Grazia Totaro, Cristina Battaglia, Anskar Yu-Hung Leung, Monica Fumagalli, Matteo Parma, Gianni Cazzaniga, Grazia Fazio, Myriam Alcalay, Anna Marozzi, Anna Pistocchi
Summary: Aberrant activation of the Hh pathway promotes cell proliferation and multi-drug resistance (MDR) in several cancers, including AML. In this study, a positive correlation between Hh, HDAC6, and MDR genes was observed in AML patients, leukemic cell lines, and a zebrafish model. Hyper-activation of Hh or HDAC6 increased proliferation of HSPCs, which could be rescued by HDAC6 inhibition. The presence of a cross-talk between Hh and HDAC6 mediated by stabilization of the primary cilium was detected for the first time. Inhibition of HDAC6 activity alone or in combination with cytarabine efficiently rescued the hematopoietic phenotype, suggesting HDAC6 as a potential therapeutic target for reducing proliferation of leukemic blasts in AML patients.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Sangwoo Shim, Raman Goyal, Alexios A. Panoutsopoulos, Olga A. Balashova, David Lee, Laura N. Borodinsky
Summary: The balance between neural stem cell proliferation and neuronal differentiation is crucial for the development of the nervous system. We found that Sonic hedgehog (Shh) enhances Ca2+ activity at the cilia of developing Xenopus laevis embryos, which promotes neuronal differentiation and inhibits proliferative signaling. These findings provide potential targets for the treatment of brain tumors and neurodevelopmental disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Marcella Barbarino, Maria Bottaro, Laura Spagnoletti, Maria Margherita de Santi, Raffaella Guazzo, Chiara Defraia, Cosimo Custoza, Gabriella Serio, Francesco Iannelli, Matilde Pesetti, Raffaele Aiello, Diletta Rosati, Edoardo Zanfrini, Luca Luzzi, Cristiana Bellan, Antonio Giordano
Summary: Primary cilium is a cellular organelle found on almost all mammalian cells, which transduces signals and regulates various physiological pathways. Dysfunction in primary cilium is associated with pathologic conditions including cancer. This study focused on the role of primary cilium in the Hedgehog signaling pathway in malignant pleural mesothelioma (MPM) and uncovered evidence of a PC-independent regulation of Hh signaling in MPM.
Review
Cell Biology
Yuhei Nishimura, Daishi Yamakawa, Takashi Shiromizu, Masaki Inagaki
Summary: The dysregulation of kinase signaling is associated with various pathological conditions like cancer and obesity. Targeting dysregulated kinases selectively in specific contexts can enhance therapeutic specificity and reduce off-target adverse effects. Primary cilia play a key role in detecting extracellular cues and their dysregulation contributes to diseases in different ways, such as cancer and ciliopathies.
Article
Biochemistry & Molecular Biology
Fatmanur Tiryaki, Jovana Deretic, Elif Nur Firat-Karalar
Summary: Centrioles and cilia are essential microtubule-based structures in cells that play critical roles in cell function and development. This study identifies a new microtubule-associated protein, ENKD1, which regulates microtubule organization and stability. Furthermore, it shows that ENKD1 depletion leads to defective regulation of ciliary length and content, as well as a failure to respond to Hedgehog pathway activation.
Article
Multidisciplinary Sciences
Lijuan Du, Alex Sohr, Yujia Li, Sougata Roy
Summary: Cytonemes, signaling filopodia in fruit flies, are found to mediate target-specific long-distance communication of FGF signals. FGF is anchored to the producing cell surface in order to inhibit free FGF secretion and promote target-specific cytoneme contacts and contact-dependent FGF release.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Adrian Aguirre-Tamaral, Isabel Guerrero
Summary: Morphogen gradients are essential for organism development, and an active transport mechanism is needed due to the biochemical properties of many morphogens. Researchers have developed an in silico model and software tool to study Hedgehog gradient formation in Drosophila tissues, demonstrating the adaptability of the model in reproducing gradients and explaining scaling differences between epithelia. They also explored the impact of various cytoneme features on Hh morphogen distribution, highlighting Cytomorph as a tool for testing different morphogen gradients and generating hypotheses that are challenging to study experimentally.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Neurosciences
C. H. H. Hor, J. C. W. Lo, A. L. S. Cham, W. Y. Leong, E. L. K. Goh
Summary: The study showed that conditional knock-out of the Shh pathway repressor Rab23 in mice resulted in mis-patterning of the cerebellum and increased GCP proliferation. Despite no prevalent occurrence of medulloblastoma in adulthood, Rab23-depleted GCPs exhibited upregulated Shh pathway activities and abnormal ciliogenesis.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Biology
Eva Cai, Jingyi Zhang, Xuecai Ge
Summary: This article reviews recent studies on the role of PKA in Hh signaling, highlighting the compartmentalization of PKA in the centrosome and primary cilium. It also outlines the genetic and optical tools that have been developed to study PKA activities during Hh signal transduction.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Review
Cell Biology
Bo Wang, Zheyong Liang, Peijun Liu
Summary: This article reviews the role of the primary cilium in cancer, including its architecture, signaling pathways, cilia assembly and disassembly regulators, summarizing new findings in tumor microenvironments and different cancers, highlighting novel possibilities for therapeutic targets in cancer.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yuhei Nishimura, Daishi Yamakawa, Katsunori Uchida, Takashi Shiromizu, Masatoshi Watanabe, Masaki Inagaki
Summary: This review highlights the importance of primary cilia and lipid rafts in signal transduction and cellular function regulation, discussing their relationship in adipogenesis and cancer biology, providing a novel research perspective.
Article
Biology
Daniel Routledge, Sally Rogers, Yosuke Ono, Lucy Brunt, Valerie Meniel, Giusy Tornillo, Hassan Ashktorab, Toby J. Phesse, Steffen Scholpp
Summary: The study demonstrates that gastric cancer cells utilize cytonemes to transport Wnt3 protein intercellularly to promote cell proliferation and survival. Additionally, the membrane-bound scaffolding protein Flotillin-2 is identified as a regulator of these cytonemes in gastric cancer.
Article
Biochemistry & Molecular Biology
Jhan-Jhang Syu, Chieh-Hsiang Chang, Pei-Yu Chang, Chia-Hsiung Liu, Chia-Jung Yu, Tzuu-Shuh Jou
Summary: The study shows that galectin 8 promotes the rapid elongation of primary cilia by binding to lipid raft components at the base of cilia and interfering with the interaction between caveolin 1 and TMEM231. The functional barrier of the transition zone is disrupted, resulting in the redistribution of cilia proteins and the elongation of primary cilia.
Article
Biology
Mengmeng Zhou, Yuhong Han, Jin Jiang
Summary: This study reveals that Ulk4 promotes Gli2 phosphorylation and activation at the ciliary tip by interacting with Stk36, suggesting a regulatory role of Ulk4 in the Hedgehog signaling pathway.
Review
Cell Biology
Julie Stoufflet, Isabelle Caille
Summary: The primary cilium plays an important role in regulating cell motility, especially in neuronal migration, by controlling the rhythm and speed of migration.
Review
Developmental Biology
Cheng Shi, Pengfei Jiao, Zhiyi Chen, Lan Ma, Siyue Yao
Summary: This review discusses the molecular etiology of congenital craniofacial abnormalities, with a focus on the role and mechanism of noncoding RNAs in regulating craniofacial development. Aberrant expression of noncoding RNAs has been implicated in the pathogenesis of craniofacial abnormalities, providing potential therapeutic targets.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Hideru Togashi, Steven Ray Davis, Makoto Sato
Summary: Tile patterns, regulated by cell adhesion molecules, are regular arrangements of cells that play important functional roles in multicellular organisms. The physical constraints and cell adhesion regulate both cell shape and tissue morphogenesis.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Armen Khanbabei, Lina Segura, Cynthia Petrossian, Aaron Lemus, Ithan Cano, Courtney Frazier, Armen Halajyan, Donnie Ca, Mariano Loza-Coll
Summary: This article investigates the genetic regulatory mechanisms of Drosophila intestinal stem cells. The study found that most target genes co-regulated by Esg and STAT show a consistent gene expression pattern. However, manipulating these validated targets in vivo rarely replicated the effects of manipulating Esg and STAT, suggesting the presence of complex genetic interactions among the downstream targets of these two master regulator genes.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Bayley J. Waters, Zoe R. Birman, Matthew R. Wagner, Julia Lemanski, Barak Blum
Summary: Researchers found that conditional deletion of Robo2 in adult mice led to a significant loss of islet architecture without affecting beta cell identity or function, suggesting that Robo2 plays a role in actively maintaining adult islet architecture. Understanding the factors required for islet architecture maintenance is crucial for developing future diabetes therapies.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Rhiannon Clements, Tyler Smith, Luke Cowart, Jennifer Zhumi, Alan Sherrod, Aidan Cahill, Ginger L. Hunter
Summary: Cell protrusions play a crucial role in regulating cell activities during development. By studying the regulation mechanism in fruit fly sensory bristle patterning, it was found that Myosin XV is essential for the dynamics of signaling filopodia and promotes long-range Notch signaling.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Margaret Keating, Ryan Hagle, Daniel Osorio-Mendez, Anjelica Rodriguez-Parks, Sarah I. Almutawa, Junsu Kang
Summary: Knock-in reporter (KI) animals are essential for studying gene expression in biomedical research. This study developed a new strategy using minicircle technology and a minimal promoter to enhance knock-in events and establish stable KI transgenic reporter lines. The study also highlighted the importance of selecting the proper KI line due to potential inappropriate influence of genome editing on reporter gene expression.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Christian Altbuerger, Meta Rath, Daniel Armbruster, Wolfgang Driever
Summary: This study reveals that Neurog1 and Olig2 transcription factors have differential requirements for the development of dopaminergic neurons, and they integrate local patterning signals and Notch neurogenic selection signaling to specify the progenitor population and initiate neurogenesis and differentiation.
DEVELOPMENTAL BIOLOGY
(2024)