Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly.
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.
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant, Spain.
Camino
C
de Juan Romero
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Carl
C
Bruder
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant, Spain.
Ugo
U
Tomasello
Service of Pathology, Hospital Universitario "Principe de Asturias", Alcalá de Henares, Spain.
José Miguel
JM
Sanz-Anquela
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant, Spain vborrell@umh.es.
Víctor
V
Borrell
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology*; D002540:Cerebral Cortex / Q000002:abnormalities / Q000033:anatomy & histology* / Q000196:embryology / Q000502:physiology*; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D005260:Female; D005289:Ferrets / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D054220:Malformations of Cortical Development / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics
D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051361:Cyclin-Dependent Kinase 6
folding; lissencephaly; microarray; protocortex; transcription factor