engleski

Transcription factor ZBTB20 as a marker for archicortical specification of developing human hippocampus

Aims: The molecular mechanisms that underlie development and regionalization of human archicortical areas, including hippocampal formation, are not fully understood. Methods: Using publicly available gene expression database of human brain (Kang et al., 2011), we selected several genes which are highly expressed in developing human hippocampus. One of them was transcription factor ZBTB20, which plays a critical role for the specification of CA1 pyramidal neurons identity (Nielsen et al., 2007). We employed immunohistochemistry on fixed-paraffin-embedded sections of postmortem human brains, ranging from the 12th postconceptional weeks (PCW) to the 6.5 years of age, to study its spatiotemporal expression pattern. Results: Expression of ZBTB20 was visible in the hippocampal primordium at 12 th PCW revealing nuclear staining in the progenitor cells of the primary dentate neuroepithelium. At 20th PCW 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. At the border between CA1 and subiculum this ZBTB20 immunoreactivity diminished and was not present in the neighboring transitional cortical areas. Between 25th and 40th PCW 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. Conclusions: Our results indicate that ZBTB20 represents a part of the regulatory molecular program of archicortical regionalization, and plays an important role for establishment of borders between archicortex, transitional cortices, and neocortex.

ZBTB20, fetal brain

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