title: Modular reorganization of the global network of gene regulatory interactions during perinatal human brain development.
abstract: BACKGROUND
  During 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.
  
  
  RESULTS
  Here 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: School of Life Sciences, University of Lincoln, Lincoln, LN6 7DL, UK.|Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Jimena
authors.initials: J
authors.lastname: Monzón-Sandoval
authors.affiliation: School of Life Sciences, University of Lincoln, Lincoln, LN6 7DL, UK.|Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Atahualpa
authors.initials: A
authors.lastname: Castillo-Morales
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK. a.urrutia@bath.ac.uk.|Milner Centre for Evolution, University of Bath, Bath, BA2 7AY, UK. a.urrutia@bath.ac.uk.
authors.forename: Araxi O
authors.initials: AO
authors.lastname: Urrutia
authors.affiliation: School of Life Sciences, University of Lincoln, Lincoln, LN6 7DL, UK. hgutierrez@lincoln.ac.uk.
authors.forename: Humberto
authors.initials: H
authors.lastname: Gutierrez
mesh_terms: D000293:Adolescent; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D005809:Genes, Regulator; D006801:Humans; D007223:Infant; D008954:Models, Biological; D011247:Pregnancy
keywords: Brain transcriptome; Gene coexpression network; Gene regulation; Human brain development