The origins of the circumventricular organs.

The circumventricular organs (CVOs) are specialised neuroepithelial structures found in the midline of the brain, grouped around the third and fourth ventricles. They mediate the communication between the brain and the periphery by performing sensory and secretory roles, facilitated by increased vascularisation and the absence of a blood-brain barrier. Surprisingly little is known about the origins of the CVOs (both developmental and evolutionary), but their functional and organisational similarities raise the question of the extent of their relationship. Here, I review our current knowledge of the embryonic development of the seven major CVOs (area postrema, median eminence, neurohypophysis, organum vasculosum of the lamina terminalis, pineal organ, subcommissural organ, subfornical organ) in embryos of different vertebrate species. Although there are conspicuous similarities between subsets of CVOs, no unifying feature characteristic of their development has been identified. Cross-species comparisons suggest that CVOs also display a high degree of evolutionary flexibility. Thus, the term 'CVO' is merely a functional definition, and features shared by multiple CVOs may be the result of homoplasy rather than ontogenetic or phylogenetic relationships.

Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.

Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB.

Anatomical, molecular and pathological consideration of the circumventricular organs.

BACKGROUND AND PURPOSE: Circumventricular organs (CVOs) are a diverse group of specialised structures characterized by peculiar vascular and position around the third and fourth ventricles of the brain. In humans, these organs are present during the fetal period and some become vestigial after birth. Some, such as the pineal gland (PG), subcommissural organ (SCO) and organum vasculosum of the lamina terminalis (OVLT), which are located around the third ventricle, might be the site of origin of periventricular tumours. In contrast to humans, CVOs are present in the adult rat and can be dissected by laser capture microdissection (LCM). METHODS: In this study, we used LCM and microarrays to analyse the transcriptomes of three CVOs, the SCO, the subfornical organ (SFO) and the PG and the third ventricle ependyma of the adult rat, in order to better characterise these organs at the molecular level. Furthermore, an immunohistochemical study of Claudin-3 (CLDN3), a membrane protein involved in forming cellular tight junctions, was performed at the level of the SCO. RESULTS: This study highlighted some potentially new or already described specific markers of these structures as Erbb2 and Col11a1 in ependyma, Epcam and CLDN3 in the SCO, Ren1 and Slc22a3 in the SFO and Tph, Anat and Asmt in the PG. Moreover, we found that CLDN3 expression was restricted to the apical pole of ependymocytes in the SCO.