Abstract
The circumventricular organs (CVOs) are small structures lining the cavities of brain ventricular system. They are associated with the semitransparent regions of the blood-brain barrier (BBB). Hence it is thought that CVOs mediate biochemical signaling and cell exchange between the brain and systemic blood. Their classification is still controversial and development not fully understood largely due to an absence of tissue-specific molecular markers. In a search for molecular determinants of CVOs we studied the green fluorescent protein (GFP) expression pattern in several zebrafish enhancer trap transgenics including Gateways (ET33-E20) that has been instrumental in defining the development of choroid plexus. In Gateways the GFP is expressed in regions of the developing brain outside the choroid plexus, which remain to be characterized. The neuroanatomical and histological analysis suggested that some previously unassigned domains of GFP expression may correspond to at least six other CVOs–the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO), paraventricular organ (PVO), pineal (epiphysis), area postrema (AP) and median eminence (ME). Two other CVOs, parapineal and subcommissural organ (SCO) were detected in other enhancer-trap transgenics. Hence enhancer-trap transgenic lines could be instrumental for developmental studies of CVOs in zebrafish and understanding of the molecular mechanism of disease such a hydrocephalus in human. Their future analysis may shed light on general and specific molecular mechanisms that regulate development of CVOs.
Highlights
It was noted that “the circumventricular organs (CVO) are peculiar brain structures that are located in the walls and often protrude in the lumen of the third and fourth ventricles (Hofer, 1958)” and that “no clear agreement can be found in the literature on the number of these organs in mammals” (Duvernoy and Risold, 2007)
One feature these regions have in common is the appearance of green fluorescent protein (GFP) expression prior to the penetration of capillaries
In the choroid plexus (CP) GFP expression encompasses at least a couple of cell types, i.e., epithelial cells of the medial cluster and astrocyte-like cells of the lateral clusters (García-Lecea et al, 2008; Figure 5A), but not the vasculature
Summary
It was noted that “the circumventricular organs (CVO) are peculiar brain structures that are located in the walls and often protrude in the lumen of the third and fourth ventricles (Hofer, 1958)” and that “no clear agreement can be found in the literature on the number of these organs in mammals” (Duvernoy and Risold, 2007). The CVOs were nicknamed “windows to the brain” (Weindl and Sofroniew, 1981; Johnson and Gross, 1993) They perform diverse functions, including, but not limited to, the exchange of information between blood, brain and cerebrospinal fluid (CSF), generation of CSF with all its specialized proteins, etc. It has been found that the CVOs, including the choroid plexus (CP), act as brain-immune interfaces mediating the transfer of immune cells from blood to brain (Shimada and Hasegawa-Ishii, 2017) This is in line with recent attempts to systematize the CVOs while considering microglia to be an important component of these structures (Oldfield and McKinley, 2014; Miyata, 2015; Kaur and Ling, 2017)
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