title: Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.
abstract: The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits.
authors: Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Brussels, Belgium.
authors: Nelle
authors: N
authors: Lambert
authors: Marie-Alexandra
authors: MA
authors: Lambot
authors: Angéline
authors: A
authors: Bilheu
authors: Valérie
authors: V
authors: Albert
authors: Yvon
authors: Y
authors: Englert
authors: Frédérick
authors: F
authors: Libert
authors: Jean-Christophe
authors: JC
authors: Noel
authors: Christos
authors: C
authors: Sotiriou
authors: Alisha K
authors: AK
authors: Holloway
authors: Katherine S
authors: KS
authors: Pollard
authors: Vincent
authors: V
authors: Detours
authors: Pierre
authors: P
authors: Vanderhaeghen
mesh_terms: D005075:Biological Evolution; D002540:Cerebral Cortex / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction