Resumo

N-myc, c-myc, L-myc are members of a proto-oncogene family encoding basic helix-loop-helix- leucine zipper (bHLHZ) proteins that regulate gene expression through a variety of mechanisms, including transcriptional activation and repression. Through the regulation of multiple target genes, Myc family proteins play crucial roles in regulating the proliferation, size, differentiation, and survival of cells during development, adulthood and tumorigenesis. Using a combination of genetics approaches, including Cre-transgenic mouse lines and Cre-expressing retrovirus, we have found that N-myc is expressed in retinal progenitor cells, where it regulates proliferation in a cell-autonomous manner. The retinae of N-myc–deficient mice are hypocellular and smaller and inactivation of N-myc affects eye growth. Objectives and Methods: In this work, we asked whether c-myc regulates mouse retinal and eye development. Nestin-Cre transgenic mice lines were used to inactivate c-myc from neural progenitors in vivo. Gene expression was analyzed by realtime RT-PCR and in situ hybridization. Retinal volume and eye growth were also measured. Results and Conclusions: As observed for N-myc, c-myc expression was detected in developing retina. c-myc gene expression levels are approximately 10 times higher in embryonic retina compared to adult, indicating that c-myc may be important during development. Both retinal progenitor cells and postmitotic retinal neurons express c-myc. Conditional inactivation of c-myc in vivo impaired retinal growth. c-myc-deficient are ~25% smaller than wild type littermates. Interestingly, simultaneous inactivation of both N-myc and c-myc induced a more severe hipoplasia then the inactivation of each member alone, suggesting that these members of Myc family may not have redundant functions in the retina. Based on our data, we propose that both N-myc and c-myc are important regulators of mice retinal and eye development. Financial Support: IBRO, IRRF, FAPERJ, CNPQ