engleski

Molecular markers of the prenatal human subthalamic nucleus

The subthalamic nucleus (STN) is an important node in the basal ganglia circuitry. The developmental origin and molecular markers of STN have been adequately studied in animal models. However, there is a need to elucidate the molecular markers guiding the development of the human STN, as this nucleus is involved in the motor, associative, and limbic functions of the cortico-basal ganglia- thalamocortical circuitry. Moreover, some transcription factors identified in the STN of experimental animals are implicated in several neurodevelopmental disorders, but the structural and molecular changes of STN’s neuronal population in these disorders were never thoroughly explored. Aims The aim of the study was to identify spatio- temporal expression patterns of transcription factors relevant for the differentiation and specification of STN’s neuronal population. Methods This study encompassed postmortem, formalin-fixed, paraffin-embedded human fetal brain tissue from the early fetal period (12-15 post-conceptional weeks, PCW) to term. Indirect immunohistochemistry with antibodies for transcription factors FOXA1, FOXP1, FOXP2, BARHL1, and PAX6 was performed on 10µm thin sections. Results We show that the developing human STN expresses transcription factors previously shown to be involved in the development of rodent STN. Moreover, the human STN expresses some transcription factors that were not previously described in animal models. Conclusions Our preliminary study accentuates the need to study the transcription factors in the developing human STN because the results from animal models cannot fully predict the human STN’s molecular markers. Elucidating the STN’s transcriptional profile could advance our understanding of its functional properties and its role in neurodevelopmental disorders.

human fetal brain ; immunohistochemistry ; subthalamic nucleus ; transcription factors

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