Despite the subdivision of the mature cerebral cortex into discrete structural/functional units, these transcription factors controlling regional fate are expressed in gradients across such subdivisions in the embryonic cortical germinal layers, raising the question of how the latter are implemented. A limited number of transcription factors have been identified to control the size, position, and area identities of cortical subdivisions, including Pa圆, Lhx2, Emx2, and Sp8 (Bishop et al, 2000 Yun et al, 2001 Sahara et al, 2007 Mangale et al, 2008 Chou et al, 2009). Cortical areas and cortical folds form during embryonic development from the cortical anlage in highly stereotyped patterns, suggesting a strong genetic regulation (Borrell & Reillo, 2012). The mammalian cerebral cortex is divided into multiple anatomical and functional areas, and in higher mammals, it is further subdivided into folds and 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. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. 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. 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.
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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.
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Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown.