engleski

Early differentiation of human central amygdaloid nucleus revealed by expression of transcription factor DLX6

Amygdala represents a heterogeneous nuclear complex consisting of morphologically different nuclei involved in various functions regarding emotional modulation. Previously, we have demonstrated a human specific transient modular organization of this structure during the mid- fetal period (Nikolic & Kostović, Anat Embryol 1986). Part of a phylogenetically older complex, central amygdaloid nucleus represents the main efferent structure projecting to many brain regions, mainly via stria terminalis and ventral amygdalofugal pathway. Here we studied possible indicators of the underlining molecular mechanisms in regional differences in maturational processes of this nuclear complex. Reviewing publicly available gene expression database of human brain (Kang et al., Nature 2011), several genes were selected which are specifically and highly expressed in human amygdala prenatally. Among them is a transcription factor Dlx6, required for molecular differentiation of striatal neurons in developing mouse brain (Wang et al, J. Comp. Neurol. 2011). To investigate DLX6 expression, we employed immunohistochemistry on fixed- paraffin-embedded sections of postmortem human brains, ranging between 15th and 28th post conception weeks (PCW). The procedure for the human autopsy material was approved and controlled by the Internal Review Board of the Ethical Committee at the School of Medicine, University of Zagreb. Expression of DLX6 was visible in the amygdaloid primordiums in the prospective central nucleus, revealing intense nuclear staining. Confocal microscopy analysis using double-staining against NeuN and GFAP revealed that DLX6+ cells colocalized with NeuN+ but not with GFAP+ cells, indicating advanced differentiation of central nucleus neurons. Our results indicate that DLX6 could be a part of the regulatory molecular program of amygdaloid regionalization, presumably playing an important role in early differentiation of the central amygdaloid nucleus. Since this nucleus represents the main efferent structure, its advanced maturation supports evidence for very early establishment of amygdaloid visceromotor circuitry.

developmental markers, amygdala differentiation, gene expression

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