Abstract
BackgroundDuring early development of the nervous system, gene expression patterns are known to vary widely depending on the specific developmental trajectories of different structures. Observable changes in gene expression profiles throughout development are determined by an underlying network of precise regulatory interactions between individual genes. Elucidating the organizing principles that shape this gene regulatory network is one of the central goals of developmental biology. Whether the developmental programme is the result of a dynamic driven by a fixed architecture of regulatory interactions, or alternatively, the result of waves of regulatory reorganization is not known.ResultsHere we contrast these two alternative models by examining existing expression data derived from the developing human brain in prenatal and postnatal stages. We reveal a sharp change in gene expression profiles at birth across brain areas. This sharp division between foetal and postnatal profiles is not the result of pronounced changes in level of expression of existing gene networks. Instead we demonstrate that the perinatal transition is marked by the widespread regulatory rearrangement within and across existing gene clusters, leading to the emergence of new functional groups. This rearrangement is itself organized into discrete blocks of genes, each targeted by a distinct set of transcriptional regulators and associated to specific biological functions.ConclusionsOur results provide evidence of an acute modular reorganization of the regulatory architecture of the brain transcriptome occurring at birth, reflecting the reassembly of new functional associations required for the normal transition from prenatal to postnatal brain development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-016-0111-3) contains supplementary material, which is available to authorized users.
Highlights
During early development of the nervous system, gene expression patterns are known to vary widely depending on the specific developmental trajectories of different structures
We examined RNA seq expression data obtained from the NIMH Transcriptional Atlas of Human Brain Development
Global changes in gene expression profiles throughout development are strictly determined by an underlying network of precise regulatory interactions between individual genes and understanding the organizing principles that define this regulatory network is one of the central goals of developmental biology
Summary
During early development of the nervous system, gene expression patterns are known to vary widely depending on the specific developmental trajectories of different structures. Elucidating the organizing principles that shape this gene regulatory network is one of the central goals of developmental biology. Development of the human nervous system is a complex and precisely regulated process that occurs over a prolonged period of time and depends on a strict temporal and regional coordination of complex patterns of gene expression. Elucidating the organizing principles that shape the whole network of gene regulatory interactions that instruct organismal development is one of the central goals of developmental biology. In this context, it is of critical important to ascertain whether the gene regulatory architecture driving. Many genes have the potential to participate in multiple separate and sometimes seemingly unrelated biological functions [5], suggesting the existence of occasional events of regulatory reassembly giving rise to the emergence of new functional associations
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