UN APPROCCIO TRASCRIZIONALE, MOLECOLARE E FUNZIONALE PER DEFINIRE L¿ONTOGENIA DEI NEURONI STRIATALI UMANI

The brain is the most complex of biological systems and our knowledge on the developmental mechanisms underlying its formation and organization have been based on studies in rodents. Little is know about the human brain development. To shed light on the telencephalic developmental program in humans we investigated the transcriptional profile that distinguish the developing striatum from the cortex and we define the molecular set that identify the different populations present in the differentiating striatum from 2 to 20 gestational weeks. This thesis represent the first description of the spatio-temporal expression profile that drive the differentiation of striatal precursors towards a medium spiny neurons fate and molecularly define the striatal compartments. New striatal determinants were identified and unexpected differences from mouse striatal development were discovered. Finally we compared the transcriptional profiles of the developing striatum and cortex with striatal and cortical primary neurons differentiated in vitro. We found an enrichment of function-related transcripts in human primary neurons that were confirmed by electrophysiological analysis revealing the presence of (i) Na+, K+ and Ca2+ currents, (ii) GABA, glutamate and dopamine receptors response and (iii) spontaneous synaptic activity.