Molecular and biochemical characterization of Sall4 function in maintaining murine embryonic stem cell pluripotency

• Antragsteller: Professor Dr. Mathias Treier
• Fachliche Zuordnung: Hämatologie, Onkologie
• Förderung: Förderung von 2008 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 65246391

Autosomal dominant mutations in the human SALL4 gene cause the human OKIHIRO or DUANE-RADIAL RAY syndrome (MIM 607323), an autosomal dominant disorder characterised phenotypically by a wide variability in acro-renal-ocular malformations. Our genetic analysis of mice with a deletion in the Sall4 gene has demonstrated that Sall4 is essential for the development and function of the inner cell mass (ICM) in mice (Elling et al. 2006, PNAS). Furthermore, we could show that in the absence of Sall4 embryonic or extra embryonic stem cell lines cannot be established from Sall4 deficient blastocysts. In contrast the ability to generate trophoblast stem cell lines from Sall4 mutant blastocysts was not impaired. Interestingly, Sall4 mutant ICMs gave rise to trophectoderm cultures. Thus, we have shown that Sall4 plays an important role in the maintenance of inner cell mass pluripotency. The goal of this research proposal is to study the role of Sall4 in maintaining embryonic stem cell pluripotency and self-renewal at the molecular and biochemical level. This should enhance our understanding of the signalling pathways and transcriptional networks underlying embryonic stem cell pluripotency and self-renewal in general and result into novel insights into the process of reprogramming of somatic genomes back to an embryonic state.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1356: Pluripotency and Cellular Reprogramming