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The neural milieu of the developing choroid plexus: neural stem cells, neurons and innervation.

Prasongchean W, Vernay B, Asgarian Z, Jannatul N, Ferretti P - Front Neurosci (2015)

Bottom Line: Furthermore, we found that extrinsic innervation is present in the developing choroid plexus, unlike previously suggested.Altogether, our data are consistent with the presence of neural progenitors within the choroid plexus, suggest that at least some of the choroid plexus neurons are born locally, and show for the first time that choroid plexus innervation occurs prenatally.Hence, we propose the existence of a complex neural regulatory network within the developing choroid plexus that may play a crucial role in modulating its function during development as well as throughout life.

View Article: PubMed Central - PubMed

Affiliation: Stem Cells and Regenerative Medicine Section, UCL Institute of Child Health, University College London London, UK ; Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University Bangkok, Thailand.

ABSTRACT
The choroid plexus produces cerebrospinal fluid and plays an important role in brain homeostasis both pre and postnatally. In vitro studies have suggested that cells from adult choroid plexus have stem/progenitor cell-like properties. Our initial aim was to investigate whether such a cell population is present in vivo during development of the choroid plexus, focusing mainly on the chick choroid plexus. Cells expressing neural markers were indeed present in the choroid plexus of chick and also those of rodent and human embryos, both within their epithelium and mesenchyme. ß3-tubulin-positive cells with neuronal morphology could be detected as early as at E8 in chick choroid plexus and their morphological complexity increased with development. Whole mount immunochemistry demonstrated the presence of neurons throughout choroid plexus development and they appeared to be mainly catecholaminergic, as indicated by tyrosine-hydroxylase reactivity. The presence of cells co-labeling for BrdU and the neuroblast marker, doublecortin, in organotypic choroid plexus cultures supported the hypothesis that neurogenesis can occur from neural precursors within the developing choroid plexus. Furthermore, we found that extrinsic innervation is present in the developing choroid plexus, unlike previously suggested. Altogether, our data are consistent with the presence of neural progenitors within the choroid plexus, suggest that at least some of the choroid plexus neurons are born locally, and show for the first time that choroid plexus innervation occurs prenatally. Hence, we propose the existence of a complex neural regulatory network within the developing choroid plexus that may play a crucial role in modulating its function during development as well as throughout life.

No MeSH data available.


Neural progenitor markers are expressed in the developing choroid plexus (CP), in different species. Unless otherwise indicated, micrographs show the CP of lateral ventricles. (A–C) E12 Chick CP stained for Sox2, transitin, and GFAP. III CP: third ventricle CP. (D–F) E12.5 mouse CP stained for pH3 (phosphorylated-histone 3), nestin, von Willebrand factor, and GFAP, either alone or in combination. Arrowheads in (D) point at proliferating cells in the CP and in the neuropepithelium (insert); only the CP is shown in (F). (G,H) Human CP at 8 weeks of gestation (CS23) stained for Sox2, nestin, and vimentin. The CP is outlined and some of the brighter SOX2-positve cells in the CP are indicated by arrowheads; note the gradient of SOX2 staining in the CP; ne, neuroepithelium. Nuclei are counterstained with Hoechst dye (blue). Scale bars are: (A) = 50 μm; (B,C) (same magnification) = 100 μm; (D,E) (same magnification) = 100 μm; (F) = 100 μm; (G) = 100 μm; (H) = 50 μm.
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Figure 1: Neural progenitor markers are expressed in the developing choroid plexus (CP), in different species. Unless otherwise indicated, micrographs show the CP of lateral ventricles. (A–C) E12 Chick CP stained for Sox2, transitin, and GFAP. III CP: third ventricle CP. (D–F) E12.5 mouse CP stained for pH3 (phosphorylated-histone 3), nestin, von Willebrand factor, and GFAP, either alone or in combination. Arrowheads in (D) point at proliferating cells in the CP and in the neuropepithelium (insert); only the CP is shown in (F). (G,H) Human CP at 8 weeks of gestation (CS23) stained for Sox2, nestin, and vimentin. The CP is outlined and some of the brighter SOX2-positve cells in the CP are indicated by arrowheads; note the gradient of SOX2 staining in the CP; ne, neuroepithelium. Nuclei are counterstained with Hoechst dye (blue). Scale bars are: (A) = 50 μm; (B,C) (same magnification) = 100 μm; (D,E) (same magnification) = 100 μm; (F) = 100 μm; (G) = 100 μm; (H) = 50 μm.

Mentions: Expression of markers of neural stem/progenitor cells, such as Sox2 and nestin, in the CP was first studied by fluorescent immunohistochemistry in sections from E12 chick brains (Figure 1 and Table 3). In the E12 CP, cells positive for the neural progenitor marker, Sox2, were detected in the CP epithelium of both lateral and 3rd ventricles (Figure 1A). The staining intensity in the CP was lower than in the neuroepithelium and a gradient of Sox2 expression, from high, in the neuroepithelium, to low, in the CP epithelium, was apparent (Figure 1A, Table 3). Interestingly, Sox2 expression in cells located at presumed CP branching points was stronger than in adjacent cells (see insert Figure 1A). The early CP epithelium was also positive for Otx2 and Pax6, and for several other markers that have been reported to be expressed in neural stem cells (Table 3). In contrast to the CP epithelium, the CP stroma was Sox2-negative. However, the CP mesenchyme contained cell expressing other neural markers, transitin, the chick nestin-like protein, and GFAP, a marker of astrocytes, radial glia and neural stem cells (Figures 1B,C). Expression of neural progenitor-associated proteins in the chick CP was consistent with expression of their transcripts detected by RT-PCR (Figure 2).


The neural milieu of the developing choroid plexus: neural stem cells, neurons and innervation.

Prasongchean W, Vernay B, Asgarian Z, Jannatul N, Ferretti P - Front Neurosci (2015)

Neural progenitor markers are expressed in the developing choroid plexus (CP), in different species. Unless otherwise indicated, micrographs show the CP of lateral ventricles. (A–C) E12 Chick CP stained for Sox2, transitin, and GFAP. III CP: third ventricle CP. (D–F) E12.5 mouse CP stained for pH3 (phosphorylated-histone 3), nestin, von Willebrand factor, and GFAP, either alone or in combination. Arrowheads in (D) point at proliferating cells in the CP and in the neuropepithelium (insert); only the CP is shown in (F). (G,H) Human CP at 8 weeks of gestation (CS23) stained for Sox2, nestin, and vimentin. The CP is outlined and some of the brighter SOX2-positve cells in the CP are indicated by arrowheads; note the gradient of SOX2 staining in the CP; ne, neuroepithelium. Nuclei are counterstained with Hoechst dye (blue). Scale bars are: (A) = 50 μm; (B,C) (same magnification) = 100 μm; (D,E) (same magnification) = 100 μm; (F) = 100 μm; (G) = 100 μm; (H) = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4379892&req=5

Figure 1: Neural progenitor markers are expressed in the developing choroid plexus (CP), in different species. Unless otherwise indicated, micrographs show the CP of lateral ventricles. (A–C) E12 Chick CP stained for Sox2, transitin, and GFAP. III CP: third ventricle CP. (D–F) E12.5 mouse CP stained for pH3 (phosphorylated-histone 3), nestin, von Willebrand factor, and GFAP, either alone or in combination. Arrowheads in (D) point at proliferating cells in the CP and in the neuropepithelium (insert); only the CP is shown in (F). (G,H) Human CP at 8 weeks of gestation (CS23) stained for Sox2, nestin, and vimentin. The CP is outlined and some of the brighter SOX2-positve cells in the CP are indicated by arrowheads; note the gradient of SOX2 staining in the CP; ne, neuroepithelium. Nuclei are counterstained with Hoechst dye (blue). Scale bars are: (A) = 50 μm; (B,C) (same magnification) = 100 μm; (D,E) (same magnification) = 100 μm; (F) = 100 μm; (G) = 100 μm; (H) = 50 μm.
Mentions: Expression of markers of neural stem/progenitor cells, such as Sox2 and nestin, in the CP was first studied by fluorescent immunohistochemistry in sections from E12 chick brains (Figure 1 and Table 3). In the E12 CP, cells positive for the neural progenitor marker, Sox2, were detected in the CP epithelium of both lateral and 3rd ventricles (Figure 1A). The staining intensity in the CP was lower than in the neuroepithelium and a gradient of Sox2 expression, from high, in the neuroepithelium, to low, in the CP epithelium, was apparent (Figure 1A, Table 3). Interestingly, Sox2 expression in cells located at presumed CP branching points was stronger than in adjacent cells (see insert Figure 1A). The early CP epithelium was also positive for Otx2 and Pax6, and for several other markers that have been reported to be expressed in neural stem cells (Table 3). In contrast to the CP epithelium, the CP stroma was Sox2-negative. However, the CP mesenchyme contained cell expressing other neural markers, transitin, the chick nestin-like protein, and GFAP, a marker of astrocytes, radial glia and neural stem cells (Figures 1B,C). Expression of neural progenitor-associated proteins in the chick CP was consistent with expression of their transcripts detected by RT-PCR (Figure 2).

Bottom Line: Furthermore, we found that extrinsic innervation is present in the developing choroid plexus, unlike previously suggested.Altogether, our data are consistent with the presence of neural progenitors within the choroid plexus, suggest that at least some of the choroid plexus neurons are born locally, and show for the first time that choroid plexus innervation occurs prenatally.Hence, we propose the existence of a complex neural regulatory network within the developing choroid plexus that may play a crucial role in modulating its function during development as well as throughout life.

View Article: PubMed Central - PubMed

Affiliation: Stem Cells and Regenerative Medicine Section, UCL Institute of Child Health, University College London London, UK ; Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University Bangkok, Thailand.

ABSTRACT
The choroid plexus produces cerebrospinal fluid and plays an important role in brain homeostasis both pre and postnatally. In vitro studies have suggested that cells from adult choroid plexus have stem/progenitor cell-like properties. Our initial aim was to investigate whether such a cell population is present in vivo during development of the choroid plexus, focusing mainly on the chick choroid plexus. Cells expressing neural markers were indeed present in the choroid plexus of chick and also those of rodent and human embryos, both within their epithelium and mesenchyme. ß3-tubulin-positive cells with neuronal morphology could be detected as early as at E8 in chick choroid plexus and their morphological complexity increased with development. Whole mount immunochemistry demonstrated the presence of neurons throughout choroid plexus development and they appeared to be mainly catecholaminergic, as indicated by tyrosine-hydroxylase reactivity. The presence of cells co-labeling for BrdU and the neuroblast marker, doublecortin, in organotypic choroid plexus cultures supported the hypothesis that neurogenesis can occur from neural precursors within the developing choroid plexus. Furthermore, we found that extrinsic innervation is present in the developing choroid plexus, unlike previously suggested. Altogether, our data are consistent with the presence of neural progenitors within the choroid plexus, suggest that at least some of the choroid plexus neurons are born locally, and show for the first time that choroid plexus innervation occurs prenatally. Hence, we propose the existence of a complex neural regulatory network within the developing choroid plexus that may play a crucial role in modulating its function during development as well as throughout life.

No MeSH data available.