pluripotency; posttranscriptional regulation; stem cells; germ cells; development
Aeschimann Florian, Kumari Pooja, Bartake Hrishikesh, Gaidatzis Dimos, Xu Lan, Ciosk Rafal, Großhans Helge (2017), LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms., in Molecular cell
, 65(3), 476-489.
Arnold Andreas, Rahman Md Masuder, Lee Man Chun, Muehlhaeusser Sandra, Katic Iskra, Gaidatzis Dimos, Hess Daniel, Scheckel Claudia, Wright Jane E, Stetak Attila, Boag Peter R, Ciosk Rafal (2014), Functional characterization of C. elegans Y-box-binding proteins reveals tissue-specific functions and a critical role in the formation of polysomes., in Nucleic acids research
, 42(21), 13353-69.
Tocchini Cristina, Keusch Jeremy J, Miller Sarah B, Finger Susanne, Gut Heinz, Stadler Michael B, Ciosk Rafal (2014), The TRIM-NHL protein LIN-41 controls the onset of developmental plasticity in Caenorhabditis elegans., in PLoS genetics
, 10(8), 1004533-1004533.
Daubner Gerrit M, Brümmer Anneke, Tocchini Cristina, Gerhardy Stefan, Ciosk Rafal, Zavolan Mihaela, Allain Frédéric H-T (2014), Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1., in Nucleic acids research
, 42(12), 8092-105.
The molecular mechanisms underlying cell fate commitment and reprogramming are fundamental for development. A profound reprogramming takes place during reproductive (germ) cell development, which is why germ cells and the various pluripotent cell lines derived from them have been invaluable for dissecting the mechanisms controlling developmental plasticity, or totipotency. Ultimately, re-launching totipotency during the oocyte-to-embryo transition is critical for the life cycle to continue. The goal of this proposal is to elucidate the molecular mechanisms controlling totipotency during animal development. To do this, we have developed a genetically tractable, rapid invertebrate model to study mechanisms controlling developmental potential of germ cells. In contrast to the much-publicized transcriptional regulation of developmental plasticity, the role of posttranscriptional regulation has been largely neglected, despite the fact that the posttranscriptional regulation is essential during gametogenesis and the oocyte-to-embryo transition, i.e. at the stages when totipotency is unleashed. My previous research demonstrated that a conserved RNA-binding protein (RBP), GLD-1, is a key regulator of totipotency in the C. elegans germ line. In gld-1 mutants, germ cells abnormally differentiate into a variety of somatic cells. These cells form the invertebrate equivalent of a human germ cell tumor known as teratoma, in which germ cells differentiate into diverse types of somatic cells and structures such as bone or teeth. For the purpose of this proposal, we refer to this ‘worm teratoma’ as the germ line-to-soma transition (GST). In the past few years, my lab quantitatively dissected GLD-1 interactions with mRNA targets and described the effects of GLD-1 on the germline transcriptome. We also made a big step towards understanding the role of GLD-1 in controlling GST, providing a possible explanation for the etiology of teratomas. However, our understanding of the mechanisms controlling totipotency remains far from complete. One future goal is to understand the precise functions of GST regulatory proteins, including GLD-1 and a new factor recently identified in the lab, the TRIM-NHL domain protein LIN-41. This goal involves dissecting both the relevant targets of these proteins and the molecular mechanisms that they utilize. GLD-1 and LIN-41 are posttranscriptional regulators, but, somehow, they control transcriptional reprogramming. Thus, another goal is to understand the molecular connection between the posttranscriptional and transcriptional regulation in controlling GST. Finally, in order to understand the pathways controlling totipotency, the relationship between GLD-1 and LIN-41 will be examined.