Article
Medicine, Research & Experimental
Harleen Kaur, Anjeza Erickson, Regis Moreau
Summary: mTORC1 plays a differential role in the immune responses of THP-1-derived macrophages and Caco-2 epithelial cells in a pro-inflammatory microenvironment, impacting cytokine gene expression through manipulation of mTORC1 activity.
Article
Biochemistry & Molecular Biology
Takahiro Suzuki, Jeremy Cheret, Fernanda Dinelli Scala, Aysun Akhundlu, Jennifer Gherardini, Dana-Lee Demetrius, James D. B. O'Sullivan, Gorana Kuka Epstein, Alan J. Bauman, Constantinos Demetriades, Ralf Paus
Summary: Dysregulation of mTORC1 activity is closely related to aging, cancer, and genetic disorders. In this study, the role of mTORC1 in human hair follicles was investigated, revealing its negative regulation on hair growth and pigmentation. Inhibition of mTORC1 stimulated hair follicle growth and pigmentation, while knockdown of the TSC2 gene reduced pigmentation. These findings suggest that pharmacological inhibition of mTORC1 could be a potential strategy for managing hair loss and depigmentation disorders.
Article
Medicine, General & Internal
Marie Monaghan, Pooja Takhar, Luke Langlands, Markus Knuf, Sam Amin
Summary: Tuberous Sclerosis Complex (TSC) is a genetic condition that results in the loss of inhibition of cellular growth. Facial angiofibromas (FAs) are hamartomatous growths associated with TSC that appear as multiple small, erythematous papules on the skin of the face and may have psychosocial impacts such as anxiety and depression. A survey study found that FAs have an impact on quality of life and psychosocial well-being for TSC patients with moderate or severe FAs.
FRONTIERS IN MEDICINE
(2022)
Article
Clinical Neurology
Krzysztof Sadowski, Kamil Sijko, Dorota Domanska-Pakiela, Julita Borkowska, Dariusz Chmielewski, Agata Ulatowska, Sergiusz Jozwiak, Katarzyna Kotulska
Summary: Rapamycin can be used to treat drug-resistant epilepsy in children with TSC, and can effectively reduce the frequency of seizures at a certain dosage. The combination with vigabatrin has better efficacy.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Mehmet Neset ozel, Felix Simon, Shadi Jafari, Isabel Holguera, Yen-Chung Chen, Najate Benhra, Rana Naja El-Danaf, Katarina Kapuralin, Jennifer Amy Malin, Nikolaos Konstantinides, Claude Desplan
Summary: Deciphering neuronal diversity in the Drosophila optic lobe during pupal development reveals transient extrinsic neurons and dorsoventral asymmetry in visual circuits.
Article
Biology
Elia Benito-Gutierrez, Giacomo Gattoni, Manuel Stemmer, Silvia D. Rohr, Laura N. Schuhmacher, Jocelyn Tang, Aleksandra Marconi, Gaspar Jekely, Detlev Arendt
Summary: The study reveals overlapping expression of conserved transcription factors that specify the telencephalon in vertebrates in the chordate amphioxus. Specific co-expression is observed in the dorsal part of the anterior brain vesicle, referred to as Pars anterodorsalis (PAD). This suggests homology between the adult amphioxus brain vesicle PAD and the vertebrate telencephalon.
Article
Biochemistry & Molecular Biology
Bartlomiej Pawlik, Szymon Grabia, Urszula Smyczynska, Wojciech Fendler, Izabela Drozdz, Ewa Liszewska, Jacek Jaworski, Katarzyna Kotulska, Sergiusz Jozwiak, Wojciech Mlynarski, Joanna Trelinska
Summary: This study suggests that miRNA dysregulation plays a role in the pathogenesis of TSC, with certain miRNAs potentially serving as markers for treatment efficacy and targets for future therapy. Results also indicate common genes targeted by the dysregulated miRNAs, although no changes in mRNA expression of these targets were observed after rapamycin treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Lin Wan, Wen He, Yang-Yang Wang, Yong Xu, Qian Lu, Meng-Na Zhang, Qiu-Hong Wang, Shuo Dun, Li-Ying Liu, Xiu-Yu Shi, Jing Wang, Lin-Yan Hu, Bo Zhang, Guang Yang, Li-Ping Zou
Summary: This study observed the occurrences of vigabatrin-associated brain abnormalities in patients with infantile spasms and explored the risk factors. The results showed a significantly lower incidence of these abnormalities in patients with tuberous sclerosis complex, and the use of rapamycin was associated with a lower risk.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2022)
Article
Anatomy & Morphology
Taiki Katsuyama, Minori Kadoya, Manabu Shirai, Noriaki Sasai
Summary: Sox14 transcription factor plays a crucial role in promoting neuronal differentiation in the chick neural tube, acting as a modulator of cell proliferation. Its expression is initially in the progenitor regions before becoming confined to the V2a region, where it is involved in regulating the differentiation of neurons. Overexpression of Sox14 restricts progenitor cell proliferation, while blocking its expression inhibits neuronal differentiation in the V2a region.
DEVELOPMENTAL DYNAMICS
(2022)
Review
Neurosciences
Tadayuki Shimada, Kanato Yamagata
Summary: Tuberous sclerosis complex (TSC) is associated with the activation of Rheb1, which affects dendritic spine morphology and synaptic structure, leading to symptoms such as epilepsy, intellectual disability, and autism.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Hirofumi Kashii, Shinya Kasai, Atsushi Sato, Yoko Hagino, Yasumasa Nishito, Toshiyuki Kobayashi, Okio Hino, Masashi Mizuguchi, Kazutaka Ikeda
Summary: The study found that double mutations in the TSC1 and TSC2 genes lead to the occurrence of autism spectrum disorder, similar to TSC2 mutations. The double mutations cause significant changes in gene expression and contribute to the genotype-phenotype correlations in TSC.
Review
Pharmacology & Pharmacy
Diem-Phuong D. Dao, Jessica N. Pixley, Zeynep M. Akkurt, Steven R. Feldman
Summary: This article evaluates the effectiveness, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for treating tuberous sclerosis complex (TSC)-associated facial angiofibromas. The gel showed improvement in tumor size and redness without any serious adverse events. It is considered a safe and effective noninvasive alternative to surgical procedures for TSC-related angiofibromas.
ANNALS OF PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Harleen Kaur, Regis Moreau
Summary: The study demonstrated that curcumin and its combination with piperine can suppress mTORC1 kinase activity, reduce inflammatory response of THP-1 macrophages, and inhibit M1 and M2 polarization signaling pathways. Curcumin also modulated monocyte differentiation into M0 macrophage phenotype with low inflammatory cytokine output.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Immunology
Ayla Batu Ozturk, Nail Can Ozturk, Furkan Ayaz
Summary: Many neurodegenerative diseases show neuroinflammation and impaired neuron production in the hippocampus. Immunotherapeutic strategies targeting microglia may be problematic. Instructing monocytes/macrophages from the periphery could be a less invasive strategy. However, the interaction between CNS neurons and macrophages is poorly understood.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Simone Bonazzi, Audrey Gray, Noel M. Thomsen, Jonathan Biag, Nancy Labbe-Giguere, Erin P. Keaney, Hasnain A. Malik, Yingchuan Sun, Jill Nunez, Rajeshri G. Karki, Mark Knapp, Robert Elling, John Fuller, Gwynn Pardee, Lucas Craig, Ketthsy Capre, Sarah Salas, Aakruti Gorde, Guiqing Liang, Danuta Lubicka, Stephanie M. McTighe, Carleton Goold, Shanming Liu, Lin Deng, Jin Hong, Alexander Fekete, Pascal Stadelmann, Wilfried Frieauff, Azeddine Elhajouji, Daniel Bauer, Andreas Lerchner, Branko Radetich, Pascal Furet, Grazia Piizzi, Doug Burdette, Christopher J. Wilson, Stefan Peukert, Lawrence G. Hamann, Leon O. Murphy, Daniel Curtis
Summary: The allosteric inhibitor everolimus reduces seizures in TSC patients by partially inhibiting mTOR functions. However, it has limited brain permeability, so a catalytic mTOR inhibitor optimized for CNS indications was developed. Compound 1 showed genotoxicity risk, but compounds 9 and 11 without genotoxicity risk successfully corrected aberrant mTOR activity and improved the survival rate in the Tsc1 gene knockout model. Unfortunately, compounds 9 and 11 had limited oral exposures and dose-limiting toxicities in cynomolgus macaque, but they remain useful for studying mTOR hyperactivity in CNS disease models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Ioannis Kasioulis, Raman M. Das, Kate G. Storey
Article
Developmental Biology
Laure Verrier, Lindsay Davidson, Marek Gierlinski, Alwyn Dady, Kate G. Storey
Article
Developmental Biology
Ioannis Kasioulis, Kate G. Storey
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
(2018)
Article
Developmental Biology
Ioanna Mastromina, Laure Verrier, Joana Clara Silva, Kate G. Storey, J. Kim Dale
Article
Developmental Biology
Aida Rodrigo Albors, Pamela A. Halley, Kate G. Storey
Article
Anatomy & Morphology
Marco A. Canizares, Aida Rodrigo Albors, Gail Singer, Nicolle Suttie, Metka Gorkic, Paul Felts, Kate G. Storey
JOURNAL OF ANATOMY
(2020)
Article
Biochemistry & Molecular Biology
Nadege Poncet, Pamela A. Halley, Christopher Lipina, Marek Gierlinski, Alwyn Dady, Gail A. Singer, Melanie Febrer, Yun-Bo Shi, Terry P. Yamaguchi, Peter M. Taylor, Kate G. Storey
Article
Biochemistry & Molecular Biology
Christine M. Tait, Kavitha Chinnaiya, Elizabeth Manning, Mariyam Murtaza, John-Paul Ashton, Nicholas Furley, Chris J. Hill, C. Henrique Alves, Jan Wijnholds, Kai S. Erdmann, Andrew Furley, Penny Rashbass, Raman M. Das, Kate G. Storey, Marysia Placzek
Article
Chemistry, Medicinal
Roman Li, Anze Zupanic, Marja Talikka, Vincenzo Belcastro, Sumit Madan, Jens Doerpinghaus, Colette vom Berg, Justyna Szostak, Florian Martin, Manuel C. Peitsch, Julia Hoeng
CHEMICAL RESEARCH IN TOXICOLOGY
(2020)
Article
Genetics & Heredity
Roman A. Li, Marja Talikka, Sylvain Gubian, Colette vom Berg, Florian Martin, Manuel C. Peitsch, Julia Hoeng, Anze Zupanic
Summary: Adverse outcomes from chemical toxicity are often caused by system-level perturbations in molecular event networks rather than individual protein dysregulation. Understanding toxicity mechanisms requires recognizing interactions of molecules, pathways, and biological processes within these networks. The developing brain, a highly complex network, presents challenges in developmental neurotoxicity, which can be addressed through the use of systems toxicology methods like computable biological networks.
FRONTIERS IN GENETICS
(2021)
Editorial Material
Developmental Biology
Sally Lowell, Alistair Downie, Holly Shiels, Kate Storey
Article
Biology
Alwyn Dady, Lindsay Davidson, Pamela A. Halley, Kate G. Storey
Summary: In vitro human neural differentiation is governed by cell intrinsic properties, but extrinsic signals are required for timely progression through the differentiation program.
Article
Cell Biology
Ioannis Kasioulis, Alwyn Dady, John James, Alan Prescott, Pamela A. Halley, Kate G. Storey
Summary: This study uncovers a new form of cell-cell contact within the developing neuroepithelium, which plays important roles in cell and tissue morphology and cell signalling.
JOURNAL OF CELL SCIENCE
(2022)
Article
Cell Biology
Aida Rodrigo Albors, Gail A. Singer, Enric Llorens-Bobadilla, Jonas Frisen, Andrew P. May, Chris P. Ponting, Kate G. Storey
Summary: The potential of adult spinal cord stem cells is found in ependymal cells, which decreases with age. Ependymal cells are heterogeneous and their biological diversity and age-related changes are still unknown. This study provides a single-cell transcriptomic census of spinal cord ependymal cells in adult and aged mice, identifying various cell subtypes and immature as well as mature cell states. It also reveals immature cells as potential spinal cord stem cells by comparing their transcriptomes with brain ependymal cells. The study further explores ependymal cells in human spinal cord and uncovers widespread cell maturation and altered cell identities. This comprehensive characterization of spinal cord ependymal cells offers insights into their biology and informs strategies for spinal cord repair.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Claudia Semprich, Lindsay Davidson, Adriana Amorim Torres, Harshil Patel, James Briscoe, Vicki Metzis, Kate G. Storey
Summary: FGF signalling decline promotes global changes in chromatin accessibility and TF binding at neural genes by directing polycomb and other regulators, serving as a gating mechanism that provides directionality to the process of differentiation.
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)