Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly

• Published in: The EMBO journal Vol. 34; no. 14; pp. 1859 - 1874
• Main Authors: de Juan Romero, Camino, Bruder, Carl, Tomasello, Ugo, Sanz-Anquela, José Miguel, Borrell, Víctor
• Format: Journal Article
• Language: English
• Published: London Blackwell Publishing Ltd 14.07.2015; Nature Publishing Group UK; John Wiley & Sons, Ltd
• Subjects: Animals; Animals, Newborn; Brain - embryology; Cerebral Cortex - abnormalities; Cerebral Cortex - anatomy & histology; Cerebral Cortex - embryology; Cerebral Cortex - physiology; Cyclin-Dependent Kinase 6 - genetics; EMBO11; EMBO27; Female; Ferrets - embryology; Ferrets - genetics; Ferrets - growth & development; folding; Gene expression; Gene Expression Regulation, Developmental; Humans; lissencephaly; Malformations of Cortical Development - genetics; Medicin och hälsovetenskap; microarray; Molecular biology; Neurology; Oligonucleotide Array Sequence Analysis; Organ Size; Pregnancy; protocortex; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Resource; transcription factor; transcription factor; lissencephaly; microarray; protocortex; folding
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.15252/embj.201591176

Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large‐scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ~80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. Synopsis Complex patterns of gene expression emerge in germinal layers during early cortical development of gyrencephalic animals. These modular expression patterns map the eventual location of folds and fissures. Microarray analysis of developing ferret cerebral cortex reveals transcriptomic differences between prospective folds and fissures. Differential gene expression delineates mosaic patterns along proliferative zones prior to the emergence of folds. Some mosaics of gene expression correlate with the prospective location of folds versus fissures. Differentially expressed genes in our microarray analysis include 80% of those mutated in human cortical malformations. Graphical Abstract Complex patterns of gene expression emerge in germinal layers during early cortical development of gyrencephalic animals. These modular expression patterns map the eventual location of folds and fissures.