Preliminary data suggests that in spite of the apparent multi-specific nature of cortex and brain development including numerous events of neuron growth, synapses establishment, connections increase, neurons elimination, etc., there exists gene-dependent and pre-programmed determinants that govern that general cortex development. This raises a possibility that one can elucidate the general mechanisms of gene regulation leading to cortex development and eventually to the brain-mine transition.
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 demonstrated 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 transcription factors” 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 revealed 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.
The overall approach contains a combination of morphological studies of brain development, which is conducted by Prof. Jean Pierre Changeux in Paris, and non-extensive entropy studies of the parameters extracted from the morphological and gene-network studies of brain system and computational analysis of existing gene expression data for brain development which are conducted by Drs. Igor F. Tsigelny, Valentina L. Kouznetsova and Michael V. Baitaluk from UCSD.