2. Interrogating neurodevelopment events by functional genomics

The evolution of genomics analyses, notably due to the sequencing of the human genome, allowed to study neurodevelopment from a different perspective; i.e., by the interrogation of the role of the genetic context during neurodevelopment. In fact, while the implication of genes in this process was previously studied at the individual level with the use of in-situ hybridization and RT-PCR methods, the developments in DNA microarray and RNA-sequencing technologies provided a global perspective as witnessed by the various studies focused on the brain transcriptome either from the whole organ or particular regions and across stages of development. Among them, the work, performed by Kang et al., for the establishment of transcriptomes from 57 postmortem human brains in 16 regions across the lifespan spanning developmental embryos through adulthood corresponds to one of the earliest most comprehensive studies. In fact, beyond the large amounts of data, they provided a spatiotemporal transcriptome regulation view enhanced by the establishment of gene co-expression networks recapitulating different stages of development. Importantly, this study highlighted that the majority of spatiotemporal differences happen before the birth with a shift of gene expression patterns around the birth in the neocortex. Principally in the fetal brain, genes with a role in cell proliferation, cell migration, and neuronal differentiation are expressed in contrast to the late fetal period and infancy, where genes coding to dendrite and synapse development are found [4].

Further studies performed by Colantuoni et al. focused on the temporal dynamic of the transcriptome in prefrontal cortex in a large number of human brain samples demonstrated that genes expressed differently in prenatal brain fetal development are reversed during postnatal life [5] with the recruitment of new genes in the early developmental brain [6]. With the same idea, the pattern of spatial gene expression in brain was shown to follow a way determined by embryonic origin that can change during development [7]. In fact, Pletikos et al. defined three phases in neocortical development: the prenatal with highest differential gene expression, the preadolescent phase with increasing synchronization of areal transcriptome, and
