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β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells

BACKGROUND: Wnts are a family of secreted signaling molecules involved in a number of developmental processes including the establishment of cell fate, polarity and proliferation. Recent studies also implicate wnts in epithelial adult stem cell maintenance, renewal and differentiation. Wnts transduc...

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Autores principales: Usongo, Macalister, Farookhi, Riaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465187/
https://www.ncbi.nlm.nih.gov/pubmed/22682531
http://dx.doi.org/10.1186/1471-213X-12-17
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author Usongo, Macalister
Farookhi, Riaz
author_facet Usongo, Macalister
Farookhi, Riaz
author_sort Usongo, Macalister
collection PubMed
description BACKGROUND: Wnts are a family of secreted signaling molecules involved in a number of developmental processes including the establishment of cell fate, polarity and proliferation. Recent studies also implicate wnts in epithelial adult stem cell maintenance, renewal and differentiation. Wnts transduce their signal through one of three signaling pathways. The best studied, the wnt/β-catenin pathway, leads to an increase in intracellular β-catenin which acts as a co-transcription factor with members of the Tcf/Lef family. A number of wnts are expressed in the ovary, specifically in the membrana granulosa and ovarian surface epithelium (OSE). We investigated the spatio-temporal pattern of β-catenin/Tcf expression in the OSE using responsive transgenic (TopGal) mice. RESULTS: The generated β-galactosidase response (lacZ(+)) identified the cell population that overlies the medio-lateral surface of the indifferent gonad at embryonic day (E) 11.5. From E12.5 onwards, lacZ expression disappeared in cells covering the testis but remained with ovary development. LacZ(+) OSE cells were present throughout embryonic and postnatal ovarian development but demonstrated an age-dependent decrease to a small proportion when animals were weaned and remained at this proportion with aging. Flow cytometric (FACS) and ovarian section analyses showed lacZ(+) cells constitute approximately 20% of OSE in postnatal (day 1) mice which fell to 8% in 5 day-old animals while in prepubertal and adult mice this accounted for only 0.2% of OSE. Apoptosis was undetected in OSE of neonates and β-catenin/Tcf-signaling cells were proliferative in neonatal mice indicating that neither cell death nor proliferation failure was responsible for the proportion alteration. It appeared that lacZ(+) cells give rise to lacZ(-) cells and this was confirmed in cell cultures. The DNA-binding dye DyeCycle Violet was used to set up the side population (SP) assay aimed at identifying subpopulations of OSE cells with chemoresistance phenotype associated with ABCG2 transporter activity. FACS analysis revealed lacZ(+) cells exhibit cytoprotective mechanisms as indicated by enrichment within the SP. CONCLUSIONS: The study raises the possibility that wnt/β-catenin-signaling cells constitute a progenitor cell population and could underlie the pronounced histopathology observed for human ovarian cancer.
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spelling pubmed-34651872012-10-06 β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells Usongo, Macalister Farookhi, Riaz BMC Dev Biol Research Article BACKGROUND: Wnts are a family of secreted signaling molecules involved in a number of developmental processes including the establishment of cell fate, polarity and proliferation. Recent studies also implicate wnts in epithelial adult stem cell maintenance, renewal and differentiation. Wnts transduce their signal through one of three signaling pathways. The best studied, the wnt/β-catenin pathway, leads to an increase in intracellular β-catenin which acts as a co-transcription factor with members of the Tcf/Lef family. A number of wnts are expressed in the ovary, specifically in the membrana granulosa and ovarian surface epithelium (OSE). We investigated the spatio-temporal pattern of β-catenin/Tcf expression in the OSE using responsive transgenic (TopGal) mice. RESULTS: The generated β-galactosidase response (lacZ(+)) identified the cell population that overlies the medio-lateral surface of the indifferent gonad at embryonic day (E) 11.5. From E12.5 onwards, lacZ expression disappeared in cells covering the testis but remained with ovary development. LacZ(+) OSE cells were present throughout embryonic and postnatal ovarian development but demonstrated an age-dependent decrease to a small proportion when animals were weaned and remained at this proportion with aging. Flow cytometric (FACS) and ovarian section analyses showed lacZ(+) cells constitute approximately 20% of OSE in postnatal (day 1) mice which fell to 8% in 5 day-old animals while in prepubertal and adult mice this accounted for only 0.2% of OSE. Apoptosis was undetected in OSE of neonates and β-catenin/Tcf-signaling cells were proliferative in neonatal mice indicating that neither cell death nor proliferation failure was responsible for the proportion alteration. It appeared that lacZ(+) cells give rise to lacZ(-) cells and this was confirmed in cell cultures. The DNA-binding dye DyeCycle Violet was used to set up the side population (SP) assay aimed at identifying subpopulations of OSE cells with chemoresistance phenotype associated with ABCG2 transporter activity. FACS analysis revealed lacZ(+) cells exhibit cytoprotective mechanisms as indicated by enrichment within the SP. CONCLUSIONS: The study raises the possibility that wnt/β-catenin-signaling cells constitute a progenitor cell population and could underlie the pronounced histopathology observed for human ovarian cancer. BioMed Central 2012-06-08 /pmc/articles/PMC3465187/ /pubmed/22682531 http://dx.doi.org/10.1186/1471-213X-12-17 Text en Copyright ©2012 Usongo and Farookhi; licensee BioMed Central Ltd http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Usongo, Macalister
Farookhi, Riaz
β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
title β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
title_full β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
title_fullStr β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
title_full_unstemmed β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
title_short β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
title_sort β-catenin/tcf-signaling appears to establish the murine ovarian surface epithelium (ose) and remains active in selected postnatal ose cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465187/
https://www.ncbi.nlm.nih.gov/pubmed/22682531
http://dx.doi.org/10.1186/1471-213X-12-17
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