scholarly journals MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus

Development ◽  
2021 ◽  
Author(s):  
Karol Kaiser ◽  
Ahram Jang ◽  
Petra Kompaníkova ◽  
Melody P. Lun ◽  
Jan Prochazka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Dual Function ◽  
Loss Of Function ◽  
Conditional Deletion ◽  
Wnt5a Expression ◽  
Brain Ventricle ◽  
Canonical Wnt ◽  
Upstream Regulators ◽  
4Th Ventricle

The choroid plexus (ChP) produces cerebrospinal fluid and forms a critical brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is critical for determining fourth ventricle (4V) ChP morphogenesis and size. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at E10.5, profoundly reduced ChP size and development. However, Wnt5a expression was enriched in Foxj1-positive epithelial cells of 4V ChP plexus, and its conditional deletion in these cells affected the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical Wnt signaling via Ror1/Ror2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS transcription factors as upstream regulators of Wnt5a in the 4V ChP epithelium.

scholarly journals MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus

2020 ◽  
Author(s):  
Karol Kaiser ◽  
Ahram Jang ◽  
Melody P. Lun ◽  
Jan Procházka ◽  
Ondrej Machon ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Dual Function ◽  
Loss Of Function ◽  
Conditional Deletion ◽  
Brain Ventricle ◽  
Canonical Wnt ◽  
The Brain ◽  
Upstream Regulators ◽  
4Th Ventricle

ABSTRACTThe choroid plexus (ChP) produces cerebrospinal fluid and forms a critical barrier between the brain and the circulation. While the ChP forms in each brain ventricle, it adopts a different shape in each one and remarkably little is known about the mechanisms underlying its development. Here, we show that epithelial WNT5A is critical for determining fourth ventricle (4V) ChP morphogenesis and size. Systemic Wnt5a knockout, or forced WNT5A overexpression beginning at E10.5, profoundly reduced the size and development of ChP in all ventricles. However, conditional deletion of Wnt5a expression in Foxj1-expressing epithelial cells affected only the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical Wnt signaling via Ror1/Ror2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS1 and MEIS2 as upstream regulators of Wnt5a in the 4V ChP epithelium.

scholarly journals Canonical Wnt signaling exerts bidirectional control on choroid plexus epithelial development

2020 ◽  
Author(s):  
Arpan Parichha ◽  
Varun Suresh ◽  
Mallika Chatterjee ◽  
Aditya Kshirsagar ◽  
Lihi Ben-Reuven ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Choroid Plexus ◽  
Embryonic Stem ◽  
Mammalian Brain ◽  
Loss Of Function ◽  
Canonical Wnt Signaling ◽  
Constitutive Activation ◽  
Cortical Hem ◽  
And Function ◽  
Canonical Wnt

AbstractThe choroid plexus (CP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the CP epithelium (CPe) arises from the Wnt- and Bmp- expressing cortical hem. We examined the role of canonical Wnt signaling in CPe development and report that the mouse and human embryonic CPe expresses molecules in this pathway. Either loss of function or constitutive activation of β-catenin, a key mediator of canonical Wnt signaling, causes a profound disruption of mouse CPe development. Loss of β-catenin results in a dysmorphic CPe, while constitutive activation of β-catenin causes a loss of CPe identity and a transformation of this tissue to a hippocampal-like identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. Our results indicate that canonical Wnt signaling is required in a precisely regulated manner for normal CP development in the mammalian brain.

The secretory epithelial cells of the choroid plexus employ a novel kinesin-related protein

1998 ◽  
Vol 55 (2) ◽  
pp. 355
Author(s):  
Kevin R Rogers ◽  
Mary Griffin ◽  
Peter J Brophy
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Related Protein

scholarly journals Porcine Choroid Plexus Epithelial Cells Induce Streptococcus suis Bacteriostasis In Vitro

2004 ◽  
Vol 72 (5) ◽  
pp. 3084-3087 ◽  
Author(s):  
Rüdiger A. Adam ◽  
Tobias Tenenbaum ◽  
Peter Valentin-Weigand ◽  
Maurice Laryea ◽  
Bernd Schwahn ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Meningitis ◽  
Choroid Plexus ◽  
Host Defense ◽  
Streptococcus Suis ◽  
Active Role ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
Choroid Plexus Epithelial

ABSTRACT The involvement of the choroid plexus in host defense during bacterial meningitis is unclear. Aiming to elucidate possible antibacterial mechanisms, we stimulated primary porcine choroid plexus epithelial cells (pCPEC) with proinflammatory cytokines and challenged them with various Streptococcus suis strains. In the supernatant of gamma interferon (IFN-γ)-stimulated pCPEC, streptococcal growth was markedly suppressed. Costimulation with tumor necrosis factor alpha enhanced this bacteriostatic effect, while supplementation of l-tryptophan completely eliminated it. We also demonstrate that an activation of indoleamine 2,3-dioxygenase in the pCPEC seems to be responsible for the IFN-γ-induced bacteriostasis. This supports the hypothesis of an active role of the choroid plexus in host defense against bacterial meningitis.

Lobated nuclei in epithelial cells of the choroid plexus of young mice

1969 ◽  
Vol 29 (3-4) ◽  
pp. 218-223 ◽  
Author(s):  
George J. Dohrmann ◽  
Peter B. Herdson
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Young Mice

scholarly journals A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexa N. Lauer ◽  
Rene Scholtysik ◽  
Andreas Beineke ◽  
Christoph Georg Baums ◽  
Kristin Klose ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Choroid Plexus ◽  
Cellular Proliferation ◽  
Inflammatory Responses ◽  
Streptococcus Suis ◽  
Gene Set Enrichment Analysis ◽  
Rna Seq

Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suis-infected pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response via cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during in vitro and in vivo S. suis ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.

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