engleski

Transcription factor ZBTB20 expression during prenatal development of human hippocampus

The molecular mechanisms that underlie development and regionalization of human archicortical areas, including hippocampal formation, are not fully understood. These areas express specific molecules whose distinct pattern of expression makes them useful as markers to distinguish a specific area during the development. Using publicly available gene expression database of human brain (Kang et al., 2011), we selected several genes which are highly expressed in human hippocampus during prenatal development. One of them is transcription factor ZBTB20, which plays a critical role for the specification of CA1 pyramidal neurons identity as well as for postnatal survival of hippocampal neurons in experimental animals. For the selected candidate gene we employed immunocytochemistry on fixed-paraffin-embedded sections of postmortem human brains, ranging from the 12th postovulatory weeks (POW) to the 6.5 years of age, to study its spatiotemporal expression pattern. Expression of ZBTB20 was visible in the hippocampal primordium at 12 th POW, in the future dentate gyrus, revealing nuclear staining in the progenitor cells of the primary dentate neuroepithelium. At 20th POW this nuclear localization of Zbtb20 immunoreactivity was pronounced in the immature neurons of the dentate granule cell layer and hilar region as well as in developing pyramidal neurons in the CA1-CA3 fields. During this developmental period, Zbtb20 expression pattern was similar to neuronal nuclear protein (NeuN) expression, a marker characteristic for early differentiated postmitotic neurons. At the border between CA1 and subiculum this Zbtb20 immunoreactivity diminished and was not visible in the neighboring transitional cortical areas. Between 25th and 40th POW ZBTB20 immunostaining clearly demarcates a boundary between hippocampus from adjacent transitional cortical areas. In the early postnatal period, 1 year and 6.5 year-old child this Zbtb20 expression was not visible anymore. Our results indicate that ZBTB20 represents a part of the regulatory molecular program of archicortical regionalization, and plays an important role for establishment/maintenance of the borders between archicortex, transitional cortices, and neocortex. Since ZBTB20 is linked to several human disorders, such as autism, the obtained data will be used for setting the baseline for studying developmental abnormalities characteristic for these disorders.

ZBTB20 ; hippocampus

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