Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

Parichha, Arpan; Suresh, Varun; Chatterjee, Mallika; Kshirsagar, Aditya; Ben-Reuven, Lihi; Olender, Tsviya; Taketo, Makoto Mark; Radošević, Velena; Bobić-Rasonja, Mihaela; Trnski, Sara; Holtzman, Michael J.; Jovanov-Milošević, Nataša; Reiner, Orly; Tole, Shubha

doi:10.1038/s41467-021-27602-z

Cited by 37 publications

(36 citation statements)

References 76 publications

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“…The WNT signaling cascade is an integral part of many biological processes, including embryonic development, cell cycle regulation, inflammation, and cancer [ 2 ]. Wnt pathway components have been identified as reliable biomarkers and potential targets for cancer treatment [ 3 , 4 ]. Wnt signal transduction is divided into canonical and non-canonical ways.…”

Section: Introductionmentioning

confidence: 99%

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

et al. 2022

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Background The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/β-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of β-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). Objective Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. Methods Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. Results Wnt signaling pathways include: Wnt/β-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. Conclusion The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.

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Section: Introductionmentioning

confidence: 99%

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

et al. 2022

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“…β-Catenin (Ctnnb1) is expressed throughout the telencephalic midline neuroepithelium from E11.5 (Parichha et al, 2022, Kadowaki et al, 2007). A scRNA-seq study of E14.5 mouse cortex also identified β-Catenin to be expressed in hem progenitors, CR cells, and choroid plexus epithelium (Loo et al, 2019, GSE123335 ).…”

Section: Resultsmentioning

confidence: 99%

“…The primary antibodies used were: LEF1 (Rabbit In situ hybridization: Plasmids used to generate probes for in situ hybridization were kind gifts from Elizabeth Grove (Lmx1a, Wnt3a, Axin2), and Cliff Ragsdale (Fzd1,). The detailed procedure of in situ hybridization was previously described in (Tole & Patterson., 1995, Parichha et al, 2022.…”

Section: Micementioning

confidence: 99%

Dentate gyrus morphogenesis is regulated by β-CATENIN function in hem-derived fimbrial glia

Parichha

Datta

Suresh

et al. 2022

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The dentate gyrus, a gateway for input to the hippocampal formation, arises from progenitors in the medial telencephalic neuroepithelium adjacent to the cortical hem. Dentate progenitors navigate a complex migratory path guided by two cell populations that arise from the hem, the fimbrial glia, and Cajal-Retzius (CR) cells. Since the hem expresses multiple Wnt genes, we examined whether β-CATENIN, which mediates canonical Wnt signaling and also participates in cell adhesion, is necessary for the development of hem-derived lineages. We report that the fimbrial glial scaffold is disorganized and CR cells are mispositioned upon hem-specific disruption of β-CATENIN. Consequently, the dentate migratory stream is severely affected, and the dentate gyrus fails to form. Using selective Cre drivers, we further determined that β-CATENIN function is required in the fimbrial glial scaffold, but not in the CR cells, for guiding the dentate migration. Our findings highlight a primary requirement for β-CATENIN for the organization of the fimbrial scaffold and a secondary role for this factor in dentate gyrus morphogenesis.

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“…Thus, developing deeper knowledge of the CP-CSF interface will lead to novel routes and mechanisms for treatment of brain disorders. In this respect, further research is needed to unravel the mechanisms through which the CP might play a detrimental role in the development of neuropsychiatric disorders [ 135 ], which in turn, may open new therapeutic avenues to treat these conditions.…”

Section: Discussionmentioning

confidence: 99%

Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders

2022

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The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of a dense network of fenestrated capillary loops that help in the synthesis, secretion and circulation of cerebrospinal fluid (CSF). This unique neuroanatomical structure is comprised of arachnoid villi stemming from frond-like surface projections—that protrude into the lumen of the four cerebral ventricles—providing a key source of nutrients to the brain parenchyma in addition to serving as a ‘sink’ for central nervous system metabolic waste. In fact, the functions of the CP are often described as being analogous to those of the liver and kidney. Beyond forming a barrier/interface between the blood and CSF compartments, the CP has been identified as a modulator of leukocyte trafficking, inflammation, cognition, circadian rhythm and the gut brain-axis. In recent years, advances in molecular biology techniques and neuroimaging along with the use of sophisticated animal models have played an integral role in shaping our understanding of how the CP–CSF system changes in relation to the maturation of neural circuits during critical periods of brain development. In this article we provide an ontogenetic perspective of the CP and review the experimental evidence implicating this structure in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.

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Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

Cited by 37 publications

References 76 publications

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

Dentate gyrus morphogenesis is regulated by β-CATENIN function in hem-derived fimbrial glia

Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders

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