Previously, LIN-53 (RBBP4/7) was identified as a molecular barrier for converting germ cells into neuron-like cells in C. elegans. Its depletion allows transdifferentiation of germ cells into somatic cells such as neurons upon ectopic expression of a neuron fate-inducing transcription factor (e.g. CHE-1 or UNC-30) [1], [2]. LIN-53 is a ubiquitously expressed histone chaperone protein and has been shown executing different functions in different tissues. While characterizing its function in somatic tissues, we tested whether there is a possible genetic interaction between
lin-53 and
lin-28 during vulva development, as
lin-53 and
lin-28 are the upstream regulators of Ras signaling [3]-[5]. When we combined the loss-of-function mutant
lin-28(
n719) with
lin-53 RNAi we assumed a genetic interaction due to a synergistic enhancement of the vulva phenotype which causes multiple protrusions anterior and posterior to the vulva. Surprisingly, during genetic crosses with vulva fate marker expressing strains we discovered that the strain
lin-28(
n719) used in this study and in many other reports must harbor a secondary background mutation, which is likely to play an important role in the fate decision of the vulva cells and for the observed genetic interaction with
lin-53. Ongoing whole genome sequencing has identified a number of relevant loci for the secondary mutation and the final result concerning the identity of this background mutation will be presented during the meeting. [1] B. Tursun, T. Patel, P. Kratsios, und O. Hobert, "Direct Conversion of C. elegans Germ Cells into Specific Neuron Types", Science, Bd. 331, Nr. 6015, S. 304-308, Jan. 2011. [2] T. Patel, B. Tursun, D. P. Rahe, und O. Hobert, "Removal of Polycomb Repressive Complex 2 Makes C. elegans Germ Cells Susceptible to Direct Conversion into Specific Somatic Cell Types", Cell Rep., Bd. 2, Nr. 5, S. 1178-1186, Nov. 2012. [3] N. J. Lehrbach u. a., "LIN-28 and the poly(U) polymerase PUP-2 regulate
let-7 microRNA processing in Caenorhabditis elegans", Nat. Struct. Mol. Biol., Bd. 16, Nr. 10, S. 1016-1020, Okt. 2009. [4] X. Lu und H. R. Horvitz, "
lin-35 and
lin-53, Two Genes that Antagonize a C. elegans Ras Pathway, Encode Proteins Similar to Rb and Its Binding Protein RbAp48", Cell, Bd. 95, Nr. 7, S. 981-991, Dez. 1998. [5] S. M. Johnson u. a., "RAS Is Regulated by the
let-7 MicroRNA Family", Cell, Bd. 120, Nr. 5, S. 635-647, Marz 2005.