O papel modulador do gene AIRE - capes

cells, including human herpesvirus-infected T cells [38] and astrocytedifferentiation in rat cells [39].To the best of our knowledge, this is the first study showing gene networkreconstruction from microarray data during normal thymus development. Threenetworks were reconstructed, corresponding to a period of thymus ontogenyimportant for the differentiation of thymocytes to mature T cells, in which it waspossible to indicate gene nodes, i.e., genes establishing positive and/ornegative interactions with other genes, including self-regulation. It is subsumingthat nodes represents the main points in the control of genetic cascades.We agree with the discussion of de La Fuente that networks obtained withonly part of a genome, as is the case of the set of genes examined in this study,are still useful representation of the underlying gene regulatory structure.Accordingly, if a gene A influences the expression of gene B through the actionof gene C, but gene C is not known (or its oligo/cDNA sequence was notincluded in the microarray used), the gene network algorithm will find aregulatory effect of A on B [40].For this reason, and trying to minimize this oversight, in this study only genenodes establishing self-regulation and/or at least three interactions with othergenes and whose pathways were confirmed in the KEGG pathway data basewere selected for discussion.The significantly modulated genes during thymus ontogeny featured nodes inthe three networks establishing positive or negative interaction among them.As mentioned, 14-15 days of gestation p.c. was the most dynamic phase interms of gene interactions (Fig. 1A). Genes implicated in the calcium signalingpathway, such as the Proline-rich Gla (G-carboxyglutamic acid) polypeptide 2247