engleski

MARKER OF ADULT UPPER CORTICAL LAYERS CUX2 IS EXPRESSED IN TRANSIENT CELL POPULATIONS OF THE HUMAN FETAL BRAIN

CUX2 is considered to be an adult upper cortical layer marker. Up to now, CUX2 expression pattern in the fetal human cortex is not known, even though human cortex is straightforward to study owing to the extraordinary resolution of laminar developmental events. Due to the subtle subplate (SP) size in rodents, CUX2 is not described in SP in previous developmental studies (Nieto, Zimmer, 2004). However, Kubo et al. (2017) depicted CUX2 during late midgestational human subplate. Here we followed fetal CUX2 spatio-temporal dynamics in order to get a better understanding of histogenetic interactions during migration, cellular fate commitment, and transient lamination. CUX2 protein expression pattern was studied by immunohistochemistry and immunofluorescence on fixed-paraffin-embedded sections of postmortem human brains from 10 to 38 post-conceptional weeks (PCW), as a part of Zagreb Neuroembryological Collection. During the pre-subplate (10 and 11 PCW) and subplate formation phase (13 PCW) CUX2 positive cells were present in SP and within the upper third of marginal zone (MZ), evenly spaced in the tangential direction. Furthermore, starting at 15 PCW, we observed CUX2 positive cells in the superficial cortical plate (CP). During the midgestation stage (15-21 PCW) and subplate stationary phase (25 PCW), we observed CUX2+ cells in MZ, CP, and SP ; however proliferative VZ and SVZ were not CUX2 positive. Newborn brain (38 PCW) reveals CUX2 positivity in gyral white matter, and scattered cells in MZ of the frontal cortex, as well as distinct subcortical reactivity. Since CUX2 was present during the pre-subplate stage, when associative neurons didn’t migrate through, furthermore it was present in SP during midgestation, and in gyral white matter of a newborn when all associative neurons finished migration, we suggest that CUX2 reactive nuclei belong to postmigratory subplate neurons which are prospective projection (transient associative) neurons. Finally, CUX2 presence in the transient cell populations of developing fetal cortex, and not only in cells destined for upper layers is the reason why it may serve as a reliable indicator of distinct histogenetic events.

human cortical development, layer markers, associative neurons

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