Martin is using haploid embryonic stem cells as a unique and efficient platform for forward genetics in mammals. These cells carry a single copy of each gene. Therefore phenotypes of recessive mutations can easily be identified. Haploid ES cells enable the dissection of genetic networks in a systems wide loss of function approach. Furthermore, despite their haploid karyotype, haploid ES cells retain pluripotent character similar to their bi-parental counterparts and can differentiate into all somatic cell types. This makes haploid ES cells a powerful tool for the genetic dissection of developmental processes.
Martin applies this system to interrogate the genetic circuitries that faithfully establish and maintain cellular identity during mammalian development. The genome wide identification of genes and pathways involved in cell fate specification will contribute to a detailed mechanistic understanding of how the concerted action of genetic networks directs differentiation along a specific lineage pathway.
Leeb, M., Dietmann S., Paramor M., Niwa H., Smith AG. 2014 Genetic Exploration of the Exit from Self-Renewal using Haploid Embryonic Stem Cells. Cell Stem Cell, http://dx.doi.org/10.1016/j.stem.2013.12.00 (corresponding author)
Leeb, M., and A. Wutz. 2011. Derivation of haploid embryonic stem cells from mouse embryos. Nature. 479:131-134.
Leeb M., Walker R., Mansfield W., Nichols J., Smith AG, and Wutz A. 2012. Germline potential of parthenogenetic haploid mouse embryonic stem cells. Development 139: 1-5 (corresponding author)
Leeb, M., D. Pasini, M. Novatchkova, M. Jaritz, K. Helin, and A. Wutz. 2010. Polycomb complexes act redundantly to repress genomic repeats and genes. Genes Dev. 24:265-76.
Leeb, M., and A. Wutz. 2007. Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells. J Cell Biol. 178:219-29.