Neural stem cell phenotype of tanycyte-like ependymal cells in the circumventricular organs and central canal of adult mouse brain.

Tanycyte is a subtype of ependymal cells which extend long radial processes to brain parenchyma. The present study showed that tanycyte-like ependymal cells in the organum vasculosum of the lamina terminalis, subfornical organ and central canal (CC) expressed neural stem cell (NSC) marker nestin, glial fibrillar acidic protein and sex determining region Y. Proliferation of these tanycyte-like ependymal cells was promoted by continuous intracerebroventricular infusion of fibroblast growth factor-2 and epidermal growth factor. Tanycytes-like ependymal cells in the CC are able to form self-renewing neurospheres and give rise mostly to new astrocytes and oligodendrocytes. Collagenase-induced small medullary hemorrhage increased proliferation of tanycyte-like ependymal cells in the CC. These results demonstrate that these tanycyte-like ependymal cells of the adult mouse brain are NSCs and suggest that they serve as a source for providing new neuronal lineage cells upon brain damage in the medulla oblongata.

Origin and development of circumventricular organs in living vertebrate.

The circumventricular organs (CVOs) function by mediating chemical communication between blood and brain across the blood-brain barrier. Their origin and developmental mechanisms involved are not understood in enough detail due to a lack of molecular markers common for CVOs. These rather small and inconspicuous organs are found in close vicinity to the third and fourth brain ventricles suggestive of ancient evolutionary origin. Recently, an integrated approach based on analysis of CVOs development in the enhancer-trap transgenic zebrafish led to an idea that almost all of CVOs could be highlighted by GFP expression in this transgenic line. This in turn suggested that an enhancer along with a set of genes it regulates may illustrate the first common element of developmental regulation of CVOs. It seems to be related to a mechanism of suppression of the canonical Wnt/ ß-catenin signaling that functions in development of fenestrated capillaries typical for CVOs. Based on that observation the common molecular elements of the putative developmental mechanism of CVOs will be discussed in this review.

Immunohistochemical detectability of cerebrovascular utrophin depends on the condition of basal lamina.

Utrophin is an autosomal homologue of dystrophin. Dystrophin is a member of the dystrophin-glycoprotein complex, which is a cell surface receptor for basal lamina components. In recent opinions utrophin occurs in the cerebrovascular endothelium but not in the perivascular glia. Cerebrovascular laminin immunoreactivity can only be detected in the subpial segments of the vessels, in circumventricular organs lacking blood-brain barrier, in immature vessels and following brain lesions. In our former experience utrophin immunoreactivity showed similar phenomena to that of laminin. The present study investigates the parallel occurrence of vascular utrophin and laminin immunoreactivity in the brain tissue, especially in the circumventricular organs, and during the parallel postnatal regression of both utrophin and laminin immunoreactivity. Their cerebrovascular immunoreactivity observed in frozen sections renders plausible the role of hidden but explorable epitopes, instead of a real absence of laminin and utrophin. The laminin epitopes are supposed to be hidden due to the fusion of the glial (i.e. brain parenchymal) and vascular basal laminae (Krum et al., Exp. Neurol. 111 (1991) 151). In all cases including its post-lesion re-appearance published formerly by us, laminin immunoreactivity may be attributed to the separation of glial and vascular basal laminae. Utrophin is localized, however, intracellularly, therefore a more complex molecular mechanism is to be assumed and it remains to be investigated how structural changes of the basal lamina may indirectly affect the immunoreactivity of utrophin. The results indicate that immunoreactivity may be influenced not only by the presence or absence of macromolecules but also by their functional state.