Development of Circumventricular Organs in the Mirror of Zebrafish Enhancer-Trap Transgenics

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.

Old Friends, immunoregulation, and stress resilience

“…Given the highly selective permeability properties of the BBB, it was long assumed that cytokines are only able to pass the BBB at the circumventricular organs (CVOs), which are brain structures that lack the impermeable characteristics of the BBB. The latter include the pineal gland, parapineal organ, vascular organ of the lamina terminalis, subfornical organ, paraventricular organ, neuropituitary, median eminence, subcommissural organ, and the area postrema and the choroid plexus [ 137 ]. In support of this theory, lesion studies in rodents indicated that a disruption of specific parts of the CVOs dampens fever, induced by peripheral LPS application [ 389 ], as well as prevents peripheral IL-1β-induced HPA axis activation [ 222 ].…”

Enhancer Trapping and Annotation in Zebrafish Mediated with Sleeping Beauty, piggyBac and Tol2 Transposons

“…Tol2 transposons have been extensively applied for ET in zebrafish [22,23]. Zebrafish ET transgenics performed with the Tol2 transposon technique could be instrumental for studies of the development of the circumventricular organs in zebrafish and for understanding the molecular mechanisms of diseases such as hydrocephalus in humans [24]. Twelve zebrafish lines with a single copy and tissue- or cell-specific GFP expression were obtained using a Tol2 transposable system containing a minimal mouse metallothionein gene promoter and GFP , and one potential En element was identified [11].…”

Camel regulates development of the brain ventricular system

“…At 36 hpf, camel expression associated with the BVS is obvious. Based on cell morphology and neuroanatomical landmarks and recent analysis (García-Lecea et al 2017 ), the domain corresponding to the most anterior midbrain RP (posterior to epiphysis) corresponds to the SCO (Fig. 3 h, h’).…”

“…The ET27 transgenics (Parinov et al 2004;Kondrychyn et al 2009;García-Lecea et al 2017) express GFP in the SCO (Fig. 9a).…”