We have described a strategy to analyze the data available on brain genes expression, using the concept of coherent-gene groups controlled by transcription factors (TFs). A hierarchical model of gene-expression patterns during brain development was established that identified the genes assumed to behave as functionally coding.Analysis of the concerned signaling pathways and processes showed distinct temporal gene-expression patterns in relation with neurogenesis/synaptogenesis. We identified the hierarchical tree of TF networks that determined the patterns of genes expressed during brain development. Some 'master TFs' at the top level of the hierarchy regulated the expression of gene groups. Enhanced/decreased activity of a few master TFs may explain paradoxes raised by the genetic determination of autism-spectrum disorders and schizophrenia. Our analysis showed gene-TF networks, common or related, to these disorders that exhibited two maxima of expression, one in the prenatal and the other at early postnatal period of development, consistent with the view that these disorders originate in the prenatal period, develop in the postnatal period, and reach the ultimate neural and behavioral phenotype with different sets of genes regulating each of these periods. We proposed a strategy for drug design based upon the temporal patterns of expression of the concerned TFs. Ligands targeting specific TFs can be designed to specifically affect the pathological evolution of the mutated gene(s) in genetically predisposed patients when administered at relevant stages of brain development.Keywords: Autism-spectrum disorder, brain development, coherent-gene groups, cortex, hierarchical coherent-gene group model, hierarchical transcription-factor network, informational entropy, neurogenesis, neurotransmission, schizophrenia, self-organizing maps, signaling pathway, synaptic epigenesis, synaptogenesis Several difficulties impede our understanding of the relationships between the organization of the genome and the neural phenotype of the brain: (1) The human genome has only 22 000 structural genes and (2) the differences in sequences of mouse, rat, monkey, chimpanzee and human genomes are so small that genome evolution, as opposed to brain evolution, appears strikingly non-linear (Changeux 1983(Changeux , 2004Ebersberger et al. 2002;Jiang Z et al. 2007;Konopka et al. 2012;Liu et al. 2012). Plausible explanations for such non-linear evolution include (1) the combinatorial co-expression of genetic determinants creating networks of interacting genes accounting for normal brain development (Johnson et al. 2011;Kang et al. 2011) and its pathologies (Ben-David and Shifman 2012;Torkamani et al. 2010), (2) the length of postnatal development (13-15 years in Homo sapiens), accompanied by major increase of brain weight (about fivefold before adulthood) (Lagercrantz et al. 2010), (3) the selective stabilization and elimination (pruning) of synapses under the control of evoked or spontaneous activity elicited by interactions with the physical...
