Molecular and functional definition of the developing human striatum

Marco Onorati, Valentina Castiglioni, Daniele Biasci, Elisabetta Cesana, Ramesh Menon, Romina Vuono, Francesca Talpo, Rocio Laguna Goya, Paul A Lyons, Gaetano P Bulfamante, Luca Muzio, Gianvito Martino, Mauro Toselli, Cinthia Farina, Roger A Barker, Gerardo Biella, Elena Cattaneo

The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal genes, including those encoding transcription factors, that distinguished striatal from neocortical identities. Unexpected differences from mouse striatal development were discovered. We monitored 36 determinants at the protein level, revealing regional domains of expression and their refinement, during striatal development. We electrophysiologically profiled human striatal neurons differentiated in vitro and determined their refined molecular and functional properties. These results provide a resource and opportunity to gain global understanding of how transcriptional and functional processes converge to specify human striatal and neocortical neurons during development.