Molecular and functional definition of the developing human striatum.
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.
Department of Biosciences and Center for Stem Cell Research, Università degli Studi di Milano, Italy.
Marco
M
Onorati
Department of Biosciences and Center for Stem Cell Research, Università degli Studi di Milano, Italy.
Valentina
V
Castiglioni
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Daniele
D
Biasci
Department of Biology and Biotechnologies, University of Pavia, Pavia, Italy.
Elisabetta
E
Cesana
Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Ramesh
R
Menon
John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Romina
R
Vuono
Department of Biology and Biotechnologies, University of Pavia, Pavia, Italy.
Francesca
F
Talpo
John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Rocio
R
Laguna Goya
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Paul A
PA
Lyons
Department of Health Sciences, Università degli Studi di Milano-San Paolo Hospital, Milan, Italy.
Gaetano P
GP
Bulfamante
Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Luca
L
Muzio
Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Gianvito
G
Martino
Department of Biology and Biotechnologies, University of Pavia, Pavia, Italy.
Mauro
M
Toselli
Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.
Cinthia
C
Farina
John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Roger A
RA
Barker
Department of Biology and Biotechnologies, University of Pavia, Pavia, Italy.
Gerardo
G
Biella
Department of Biosciences and Center for Stem Cell Research, Università degli Studi di Milano, Italy.
Elena
E
Cattaneo
D000200:Action Potentials / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000196:embryology* / Q000502:physiology*; D047109:Fetal Development / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D009924:Organ Culture Techniques