"Transcriptional Control of Cell Proliferation and Differentation in development and Cancer"
The Hurlin laboratory is interested in elucidating fundamental mechanisms that regulate cell proliferation, particularly in the context of skeletal development. A major focus is the Myc family of transcription factors. Myc proteins perform critical functions in cell cycle entry and the proliferative cell cycle and promote tumor formation when deregulated/and or overexpressed in cells. The c-Myc or N-Myc proteins perform essential roles during development, as mice lacking either protein fail to survive past midgestation. We are performing mouse genetic experiments in which the c-Myc gene or the N-Myc gene is conditionally eliminated in cells that give rise to the limbs and craniofacial tissues. These experiments are providing new insights into fundamental aspects about how limbs and head structures develop. They are also providing clues about mechanisms underlying various birth defect syndromes affecting limb and craniofacial development.
In addition, we are investigating the function of several Myc-related proteins that we identified that antagonize the activities of Myc. One of these proteins, Mnt, appears to play a particularly important function as a governor of Myc activity. To investigate the relationship between Mnt and Myc, we have generated mice that contain conditional alleles for both c-Myc and Mnt and for both N-Myc and Mnt. Our results examining mouse embryonic fibroblasts lacking both Mnt and c-Myc indicate that Mnt deletion can rescue the proliferation arrest caused by deletion of c-Myc. We are now extending these studies to determine whether Mnt deletion can rescue embryonic lethality caused by c-Myc or N-Myc deletion, as well the consequences of simultaneous deletion of Mnt and Myc in specific mouse tissues. From these experiments we hope to elucidate basic mechanisms that control cell proliferation during embryogenesis and cancer.