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.

UN APPROCCIO TRASCRIZIONALE, MOLECOLARE E FUNZIONALE PER DEFINIRE L¿ONTOGENIA DEI NEURONI STRIATALI UMANI / V. Castiglioni ; tutor: E. Cattaneo ; coordinatore: A. Panerai. - : . DIPARTIMENTO DI BIOSCIENZE, 2014 Jan 16. ((26. ciclo, Anno Accademico 2013. [10.13130/castiglioni-valentina_phd2014-01-16].

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

V. Castiglioni
2014-01-16

Abstract

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.
CATTANEO, ELENA
PANERAI, ALBERTO EMILIO
human brain ; striatum ; development ; differentiation
Settore BIO/14 - Farmacologia
UN APPROCCIO TRASCRIZIONALE, MOLECOLARE E FUNZIONALE PER DEFINIRE L¿ONTOGENIA DEI NEURONI STRIATALI UMANI / V. Castiglioni ; tutor: E. Cattaneo ; coordinatore: A. Panerai. - : . DIPARTIMENTO DI BIOSCIENZE, 2014 Jan 16. ((26. ciclo, Anno Accademico 2013. [10.13130/castiglioni-valentina_phd2014-01-16].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/229426
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