O papel modulador do gene AIRE - capes
O papel modulador do gene AIRE - capes O papel modulador do gene AIRE - capes
4) Finally, Prrg2 was also identified as a gene node, which was negativelyregulated by five (Itm2b, transcribed locus ID 640711, Stxbp3a, Triobp andGosr2) of the eight gene nodes in this phase and also exhibited self-negativeregulation. However, it positively regulated the Tacc1 node.Taken together, these findings indicate that thymus ontogeny (14-17 daysof gestation) features dynamic gene networks, involving pathways implicatedin cell signaling and protein transport, including T cell receptor chains towardsthe cell membrane.However, is important to consider that the networks reconstructed in thisstudy are the result of specialized statistical microarray data analysis. Furtherinvestigations are necessary to determine their precise molecularmechanisms, i.e. involvement of RNA-RNA or DNA-RNA associationscontrolling the networks.The probabilistic gene interactions observed in this work open newperspective for further molecular/biochemical approaches to confirm the role ofgenetic cascades in thymus development.AcknowledgementsThis study was funded by the Fundação de Amparo à Pesquisa do Estadode São Paulo (FAPESP) and the Conselho Nacional de DesenvolvimentoCientífico e Tecnológico (CNPq). The cDNA clones used for preparing themicroarrays were kindly ceded by Dr. Catherine Nguyen (INSERM, URM 206,Marseille, France). We thank Guilherme Liberato Silva for help anddiscussions.253
References1. Anderson G, Moore NC, Owen JJT, Jenkinson EJ (1996) Cellular interactionsin thymocyte development. Annu Rev Immunol 14:73-992. Anderson G, Jenkinson EJ (2001) Lymphostromal interactions in thymicdevelopment and function. Nature Rev. Immunol. 1: 31-403. Kishimoto H, Sprent J, (1999) Several different cell surface molecules controlnegative selection of medullary thymocytes. J Exp Med 190: 65-734. Klein L, Kyewski B (2000) Self-antigen presentation by thymic stromal cells: asubtle division of labor. Curr Opin Immunol 12: 179-1865. Kyewski B, Derbinski J (2004) Self-representation in the thymus: an extendedview. Nat Rev Immunol 4: 688-6986. Puthier D, Joly F, Irla M, Saade M, Victorero G, Loriod B, Nguyen C (2004) Ageneral survey of thymocyte differentiation by transcriptional analysis ofknockout mouse models. J Immunol 173: 6109-61187. Magalhães DA, Macedo C, Junta CM, Mello SS, Marques MM, Cardoso RS,Sakamoto-Hojo ET, Donadi EA, Passos GA (2005) Hybridization signaturesduring thymus ontogeny reveals modulation of genes coding for T-cell signalingproteins. Mol. Immunol. 42: 1043-10488. Cardoso RS, Junta CM, Macedo C, Magalhães DA, Silveira EL, Paula MO,Marques MM, Mello SS, Zarate-Blades CR, Nguyen C, Houlgatte, Donadi EA,Sakamoto-Hojo ET, Passos GA (2006) Hybridization signatures of gammairradiatedmurine fetal thymus organ culture (FTOC) reveal modulation of genesassociated with T-cell receptor V(D)J recombination and DNA repair. MolImmunol 43: 464-4729. Eisen MB, Spellmam PT, Brown PO, Botstein D (1998) Cluster analysis anddisplay of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863-1486810. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarraysapplied to ionizing radiation response. Proc Natl Acad Sci USA 98: 5126-512111. Sousa-Cardoso R, Magalhães DA, Baião AM, Junta CM, Macedo C,Marques MM, Sakamoto-Hojo ET, Donadi EA, Passos GA (2006) Onset ofpromiscuous gene expression in fetal thymus organ culture. Immunology 119:369-37512. Wu CC, Huang HC, Juan HF, Chen ST (2004) GeneNetwork: An interactivetool for reconstruction of genetic network using microarray data. Bioinformatics20: 3691-369313. Schatz DG (2004) V(D)J recombination. Immunol Rev 200: 5-11254
- Page 218 and 219: MANUSCRITOAbstractThe expression of
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References1. Anderson G, Moore NC, Owen JJT, Jenkinson EJ (1996) Cellular interactionsin thymocyte development. Annu Rev Immunol 14:73-992. Anderson G, Jenkinson EJ (2001) Lymphostromal interactions in thymicdevelopment and function. Nature Rev. Immunol. 1: 31-403. Kishimoto H, Sprent J, (1999) Several different cell surface molecules controlnegative selection of medullary thymocytes. J Exp Med 190: 65-734. Klein L, Kyewski B (2000) Self-antigen presentation by thymic stromal cells: asubtle division of labor. Curr Opin Immunol 12: 179-1865. Kyewski B, Derbinski J (2004) Self-representation in the thymus: an extendedview. Nat Rev Immunol 4: 688-6986. Puthier D, Joly F, Irla M, Saade M, Victorero G, Loriod B, Nguyen C (2004) A<strong>gene</strong>ral survey of thymocyte differentiation by transcriptional analysis ofknockout mouse models. J Immunol 173: 6109-61187. Magalhães DA, Mace<strong>do</strong> C, Junta CM, Mello SS, Marques MM, Car<strong>do</strong>so RS,Sakamoto-Hojo ET, Donadi EA, Passos GA (2005) Hybridization signaturesduring thymus ontogeny reveals modulation of <strong>gene</strong>s coding for T-cell signalingproteins. Mol. Immunol. 42: 1043-10488. Car<strong>do</strong>so RS, Junta CM, Mace<strong>do</strong> C, Magalhães DA, Silveira EL, Paula MO,Marques MM, Mello SS, Zarate-Blades CR, Nguyen C, Houlgatte, Donadi EA,Sakamoto-Hojo ET, Passos GA (2006) Hybridization signatures of gammairradiatedmurine fetal thymus organ culture (FTOC) reveal modulation of <strong>gene</strong>sassociated with T-cell receptor V(D)J recombination and DNA repair. MolImmunol 43: 464-4729. Eisen MB, Spellmam PT, Brown PO, Botstein D (1998) Cluster analysis anddisplay of genome-wide expression patterns. Proc Natl Acad Sci USA 95:14863-1486810. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarraysapplied to ionizing radiation response. Proc Natl Acad Sci USA 98: 5126-512111. Sousa-Car<strong>do</strong>so R, Magalhães DA, Baião AM, Junta CM, Mace<strong>do</strong> C,Marques MM, Sakamoto-Hojo ET, Donadi EA, Passos GA (2006) Onset ofpromiscuous <strong>gene</strong> expression in fetal thymus organ culture. Immunology 119:369-37512. Wu CC, Huang HC, Juan HF, Chen ST (2004) GeneNetwork: An interactivetool for reconstruction of <strong>gene</strong>tic network using microarray data. Bioinformatics20: 3691-369313. Schatz DG (2004) V(D)J recombination. Immunol Rev 200: 5-11254
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