Jan Mašek

Jan Mašek
Charles University in Prague | CUNI · Department of Cell Biology (PF)

PhD

About

26
Publications
7,059
Reads
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652
Citations
Introduction
Charmed by the Wnt/b-catenin and Notch signaling pathways. Grateful to my former supervisors Dr. Bryja, Dr. Machon, Dr. Kozmik and Dr. Andersson and all the great colleagues and friends I met along the way. My current goal as a group leader is to create a thriving research hub for studies of signaling cross-talk in various contexts of vertebrate development and disease.
Additional affiliations
June 2016 - present
Karolinska Institutet
Position
  • PostDoc Position
September 2010 - May 2016
January 2010 - March 2010
Karolinska Institutet
Position
  • Visiting Student

Publications

Publications (26)
Article
Full-text available
Background & Aims Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We a...
Article
Full-text available
Generation of neurons in the embryonic neocortex is a balanced process of proliferation and differentiation of neuronal progenitor cells. Canonical Wnt signalling is crucial for expansion of radial glial cells in the ventricular zone and for differentiation of intermediate progenitors in the subventricular zone. We detected abundant expression of t...
Article
Full-text available
Genetic loss and gain of function in mice have typically been studied by using knockout or knockin mice that take months to years to generate. To address this problem for the nervous system, we developed NEPTUNE (NEural Plate Targeting by in Utero NanoinjEction) to rapidly and flexibly transduce the neural plate with virus prior to neurulation, and...
Article
Full-text available
Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across s...
Article
Full-text available
Notch signaling regulates a vast array of crucial developmental processes. It is therefore not surprising that mutations in genes encoding Notch receptors or ligands lead to a variety of congenital disorders in humans. For example, loss of function of Notch results in Adams-Oliver syndrome, Alagille syndrome, spondylocostal dysostosis and congenita...
Preprint
Full-text available
Reconstruction of heterogeneity through single-cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we implement Spatial Transcriptomics to perform transcriptomic analysis acro...
Preprint
Full-text available
Gene variants associated with disease are efficiently identified with whole genome sequencing or GWAS, but validation in vivo lags behind. We developed NEPTUNE (neural plate targeting by in utero nanoinjection), to rapidly and flexibly introduce gene expression-modifying viruses to the embryonic murine neural plate prior to neurulation, to target t...
Article
Full-text available
Embryonic neural stem cells (NSCs), comprising neuroepithelial and radial glial cells, are indispensable precursors of neurons and glia in the mammalian developing brain. Since the process of neurogenesis occurs in a hypoxic environment, the question arises of how NSCs deal with low oxygen tension and whether it affects their stemness. Genes from t...
Article
Full-text available
The neural crest (NC) is crucial for the evolutionary diversification of vertebrates. NC cells are induced at the neural plate border by the coordinated action of several signaling pathways, including Wnt/β-catenin. NC cells are normally generated in the posterior neural plate border, whereas the anterior neural fold is devoid of NC cells. Using th...
Article
Full-text available
TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a condition...
Article
Full-text available
Aberrant fibroblast growth factor (FGF) signaling disturbs chondrocyte differentiation in skeletal dysplasia, but the mechanisms underlying this process remain unclear. Recently, FGF was found to activate canonical WNT/β-catenin pathway in chondrocytes via Erk MAP kinase-mediated phosphorylation of WNT co-receptor Lrp6. Here, we explore the cellula...
Article
Full-text available
β-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/β-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the β-arrestin function in Wnt/β-catenin signaling. We demonstrate that...
Article
Full-text available
Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/β-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on E...
Data
Full-text available
Analysis FGFR3 and LRP6 transgene expression in RCS cells. (A) Cells were transfected with high amounts of either V5-tagged LRP6 (upper panel) or FGFR3 (lower panel) vectors (6 µg of plasmid per 1×105 cells), and analyzed for the indicated molecules 48 hours later. K508M - kinase inactive FGFR3 mutant. Note the high amounts of Ser1490 phosphorylati...
Data
Full-text available
Constitutively active forms of RAF, RAS and SRC signal via ERK/LRP6 pathway. (A, D) RCS cells were transfected with empty plasmid or plasmid encoding RafCAAX, RAS-V12 or SRC-Y529F, grown for 48 hours, and analyzed for indicated molecules by WB. (B, E) Cells were transfected as indicated together with Topflash firefly luciferase (F-Luc) and control...
Data
Effect of activating FGFR3 mutants on basal levels of Topflash activity. Cells were transfected with the indicated FGFR3 vectors together with Topflash firefly luciferase (F-Luc) and control Renilla luciferase (R-Luc) vectors, and analyzed for luciferase activity 48 hours later. Data represent an average from four transfections (each measured twice...
Data
Full-text available
Effect of FGF signaling on WNT/β-catenin signaling in PC12 cells. Cells were transfected with Topflash vector, the indicated FGFR3 expression plasmid, and Renilla luciferase vector at a ratio of 1∶1∶0.1. Cells were transfected with a total of 10.5 µg DNA using Lipofectamine 2000 (Invitrogen). The following day, cells were serum-starved 3 hours, tre...
Data
Full-text available
FGF2 upregulates WNT/β-catenin signaling independent of the PI3K/AKT pathway. (A) RCS cells were treated with FGF2 (10 ng/ml) for the indicated times and analyzed for activatory Ser473 phosphorylation of AKT by WB. (B) AKT was immunoprecipitated from FGF2-treated cells and used in a kinase assay with recombinant GSK3 as a substrate. C1, C2 - untrea...
Article
Full-text available
LDL-related protein 6 (LRP6) is a coreceptor of WNTs and a key regulator of the WNT/β-catenin pathway. Upon activation, LRP6 is phosphorylated within its intracellular PPPS/TP motifs. These phosphorylated motifs are required to recruit axin and to inhibit glycogen synthase kinase 3 (GSK3), two basic components of the β-catenin destruction complex....
Article
Full-text available
Dishevelled (Dvl) is a multifunctional effector of different Wnt cascades. Both canonical Wnt3a and noncanonical Wnt5a stimulate casein-kinase-1 (CK1) -mediated phosphorylation of Dvl, visualized as electrophoretic mobility shift [phosphorylated and shifted Dvl (ps-Dvl)]. However, the role of this phosphorylation remains obscure. Here we report the...

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Projects

Project (1)
Project
Dissecting the Notch receptor-ligand signaling interactions with single-cell resolution.