SPECIES - SPECIFIC EXPRESSION PATTERNS OF NKX2-1 AND PAX6 IN THE DEVELOPING MOUSE AND HUMAN STN

The subthalamic nucleus (STN) is a small subcortical structure that modulates basal ganglia output and participates in motor, associative, and limbic functions within the cortico-basal ganglia-thalamocortical network. While its developmental origin and molecular markers are well characterized in animal models, human STN ontogeny remains poorly understood. To explore this gap, we analyzed the expression of several transcription factors (TFs) reported in mouse STN, along with TFs that are important for the development of surrounding structures, like the hypothalamus and the ganglionic eminences.
We focused on NKX2-1, a key TF for hypothalamic basal plate and medial ganglionic eminence specification, and PAX6, essential for diencephalic and lateral ganglionic eminence patterning. Using indirect immunohistochemistry, we analyzed age-matched, formalin-fixed, paraffin-embedded fetal human and mouse embryonic brain tissue.
First results indicate that these two TFs mark a human–specific subpopulation, since NXK2-1 could be found in human STN postnatally, and PAX6 is also expressed only in human STN after the late fetal period. In age-matched mouse brains, there was no NXK2-1 and PAX6 expression in the STN, while expression patterns in other subcortical structures followed previously reported patterns. This study underscores the necessity of defining human-specific molecular markers to better understand STN maturation and its role in basal ganglia circuitry. Recognizing species differences in TF expression is essential for interpreting developmental data and translating findings from animal research to human neurodevelopment.
Acknowledgements: This work was supported by the Croatian Science Foundation grant no. IP-2024-05-8297 (GS).