Barchuk, Angel RCristino, Alexandre SKucharski, RobertCosta, Luciano FSimões, Zilá LPMaleszka, Ryszard2015-12-072015-12-071471213Xhttp://hdl.handle.net/1885/17062BACKGROUND In honeybees, differential feeding of female larvae promotes the occurrence of two different phenotypes, a queen and a worker, from identical genotypes, through incremental alterations, which affect general growth, and character state alterations that result in the presence or absence of specific structures. Although previous studies revealed a link between incremental alterations and differential expression of physiometabolic genes, the molecular changes accompanying character state alterations remain unknown. RESULTS By using cDNA microarray analyses of >6,000 Apis mellifera ESTs, we found 240 differentially expressed genes (DEGs) between developing queens and workers. Many genes recorded as up-regulated in prospective workers appear to be unique to A. mellifera, suggesting that the workers' developmental pathway involves the participation of novel genes. Workers up-regulate more developmental genes than queens, whereas queens up-regulate a greater proportion of physiometabolic genes, including genes coding for metabolic enzymes and genes whose products are known to regulate the rate of mass-transforming processes and the general growth of the organism (e.g., tor). Many DEGs are likely to be involved in processes favoring the development of caste-biased structures, like brain, legs and ovaries, as well as genes that code for cytoskeleton constituents. Treatment of developing worker larvae with juvenile hormone (JH) revealed 52 JH responsive genes, specifically during the critical period of caste development. Using Gibbs sampling and Expectation Maximization algorithms, we discovered eight overrepresented cis-elements from four gene groups. Graph theory and complex networks concepts were adopted to attain powerful graphical representations of the interrelation between cis-elements and genes and objectively quantify the degree of relationship between these entities. CONCLUSION We suggest that clusters of functionally related DEGs are co-regulated during caste development in honeybees. This network of interactions is activated by nutrition-driven stimuli in early larval stages. Our data are consistent with the hypothesis that JH is a key component of the developmental determination of queen-like characters. Finally, we propose a conceptual model of caste differentiation in A. mellifera based on gene-regulatory networks.This work was funded by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil, Fapesp (Proc. 99/00719-6; 2005/03926-5; 04/08928-3) to ZLPS. LdFC was supported by CNPq (308231/03-1) and FAPESP (05/00587-5). ARB was supported by postdoctoral fellowships from Fapesp (Proc. 04/03408-1 and 05/53083-4) and AdSC by doctoral fellowship from MEC-Capes (Brazil).© 2007 Barchuk et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.animalsbehavior, animalexpressed sequence tagsfemalegene expression profilinggene regulatory networksjuvenile hormoneslarvaoligonucleotide array sequence analysisbeesgene expression regulation, developmentalgenes, insecthierarchy, socialMolecular determinants of caste differentiation in the highly eusocial honeybee Apis mellifera2007-06-1810.1186/1471-213X-7-702015-12-10