Molecular characterization of circumventricular organs and third ventricle ependyma in the rat: potential markers for periventricular tumors

Abstract

Circumventricular organs (CVOs) are specialized ventricular structures around the third and fourth ventricles of the brain. In humans, these structures are present during the fetal period and some become vestigial after birth. Some of these organs, such as the pineal gland (PG), subcommissural organ (SCO), and organum vasculosum of the lamina terminalis, might be the sites of origin of periventricular tumors, notably pineal parenchymal tumors, papillary tumor of the pineal region and chordoid glioma. In contrast to the situation in humans, CVOs are present in the adult rat and can be dissected by laser capture microdissection (LCM). In this study, we used LCM and microarrays to analyze the transcriptomes of three CVOs, the SCO, the subfornical organ (SFO), and the PG and the third ventricle ependyma in the adult rat, in order to better characterize these organs at the molecular level. Several genes were expressed only, or mainly, in one of these structures, for example, Erbb2 and Col11a1 in the ependyma, Epcam and Claudin-3 (CLDN3) in the SCO, Ren1 and Slc22a3 in the SFO and Tph, Aanat and Asmt in the PG. The expression of these genes in periventricular tumors should be examined as evidence for a possible origin from the CVOs. Furthermore, we performed an immunohistochemical study of CLDN3, a membrane protein involved in forming cellular tight junctions and found that CLDN3 expression was restricted to the apical pole of ependymocytes in the SCO. This microarray study provides new evidence regarding the possible origin of some rare periventricular tumors.

Tanycyte‐like cells form a blood–cerebrospinal fluid barrier in the circumventricular organs of the mouse brain

“…Tight junctions are located at the apical pole of the ependymal cells with the typical honeycomb pattern. Our study supports the view that the SCO is sequestered within a double‐barrier system (Rodriguez et al, ) and supplements the work of Szathmari et al (), who demonstrated claudin 3 immunoreactivity in ependymal cells of the SCO. Importantly, in contrast with the ependymal cells of other CVOs, ependymal cells in the SCO display numerous cilia that coat the ventricular wall and project into the ventricular lumen (Meiniel, ).…”

Expression of thyroid transcription factor 1 in a chordoid glioma

“…Our finding if confirmed by others, may suggest a potential role of this transcription factor in the development of morphologically heterogeneous neoplasms in the third ventricular region. As recently reported [8] the exact role of TTF-1 and other potential markers in the histogenesis of sellar tumours should be further explored with molecular techniques. This should contribute to a better understanding of new tumour signalling pathways involved in these tumours and will hopefully lead to the development of targeted therapy with specific inhibitors.…”

“…There is some evidence that TTF-1 may contribute to the control of sexual maturation through activation of ErbB2, a membrane bound molecule with tyrosine kinase activity belonging to the Epithelial Growth Factor Receptor (EGFR) family [7]. Interestingly ErbB2 expression was reported recently using microarray technique in third ventricle ependyma in the rat [8]. TTF-1 is used in pathology as a diagnostic marker for the identification of metastatic lesions of thyroid and bronchial origin.…”

Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control

“…In these regions, the BBB capillaries are highly fenestrated with less tight junctions between endothelial cells creating a more permeable barrier (Bennett et al, 2009). Seven periventricular regions display differential barrier properties and are collectively known as the circumventricular organs: i, sub-fornical organ; ii, organum vasculosum of the lamina terminalis; iii, pituitary; iv, area postrema; v, median eminence (ME); vi, subcomissural organ; and vii, pineal (Bennett et al, 2009; Szathmari et al, 2013). In these regions, in addition to the cells that classically form the BBB vessels, a differential type of radial glial cell, termed tanycytes are also found in the interface between the spinal fluid and the capillaries (Rodríguez et al, 2010).…”