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.
Highlights
The choroid plexus (CP) is important for the secretion of cerebrospinal fluid (CSF) and plays an important role in brain development, homeostasis and disease
The early Choroid Plexus (CP) epithelium was positive for orthodenticle homeobox 2 (Otx2) and Pax6, and for several other markers that have been reported to be expressed in neural stem cells (Table 3)
Analysis of Choroid Plexus (CP) Organotypic Cultures expression of neural progenitor markers within the CP suggested that the Dcx-positive cells are born within the CP, it could not be ruled out that post-mitotic Dcx-positive neuroblasts had migrated into the CP from other brain regions
Summary
The choroid plexus (CP) is important for the secretion of cerebrospinal fluid (CSF) and plays an important role in brain development, homeostasis and disease. The CP epithelium, considered to be a specialized ependymal epithelium, is continuous with the ependyma lining the brain of lateral, III and IV ventricles. It originates from the neuroepithelium, whereas the inner CP stromal core is believed to originate from the mesenchyme (Lehtinen et al, 2013; Liddelow et al, 2013). The CP develops early during embryogenesis and which CP is first clearly visible depends on the species. The chick lateral ventricle CP rapidly grows, lengthening and branching out many times with a dip in its growth reported at around E15–E16 followed by its thinning and flattening (Smith, 1966; Stastny and Rychter, 1976)
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