The role of LIN 9 in early mouse development

• Applicant: Professor Dr. Stefan Gaubatz
• Subject Area: Developmental Biology
• Term: from 2008 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 78865409

E2F transcription factors and pocket-proteins are key regulators of cell proliferation, development, differentiation and apoptosis. E2F activity is regulated by binding to pRB the product of the retinoblastoma tumor-suppressor gene and by binding to two related pocketproteins p107 and p130. Genetic engineering in embryonic stem cells have allowed the generation of mouse lines lacking specific E2F factors or pocket proteins. These studies revealed tissue specific developmental phenotypes and a relative high level of redundancy among E2Fs and pocket proteins. We have recently identified LINC, a novel E2F/ pocket protein complex in mammalian cells that is related to similar complexes in invertebrates. LINC consists of a core module of five proteins and dynamically associates with E2Fs, pocket proteins and the B-MYB transcription factor during the cell cycle. The LIN9 component of LINC is essential for cell cycle progression through the G2 phase and for entry into mitosis. We have found that inactivation of LIN9 in the mouse results in early embryonic lethality at the peri-implantation stage. The aim of this proposal is to determine the cause of lethality of LIN9-deficient embryos. To address this question, we will use several different mouse models, including a mouse line harboring a conditional allele of Lin9. These studies will increase our understanding of the role of cell cycle regulation in early mammalian development.

• DFG Programme: Research Grants