Letters in 2013

The segregase Cdc48 (also called p97 or VCP) extracts ubiquitylated proteins from their environment. Jentsch and colleagues demonstrate that Cdc48 binds SUMOylated Rad52, and removes Rad52 and the recombinase Rad51 from DNA to restrict spontaneous recombination.

Haematopoietic stem cells (HSCs) emerge from a specialized population of endothelial cells, but the events that trigger the transition from endothelial to haemogenic fate are still unclear. Keller and colleagues identified Sox17 as a regulator of this transition upstream of the Notch signalling pathway. They showed that Sox17–GFP marks emerging HSCs in embryo development and when differentiating from mouse embryonic stem cells.

The mechanism of tissue maintenance in the tongue is unclear. Ueno and colleagues define Bmi1-positive stem cells in the interpapillary pit of the murine tongue and demonstrate that these cells (which exhibit low proliferative properties at homeostasis) ensure regeneration of the tongue after injury.

Adipocytes have been suggested to arise from prospective progenitors of endothelial or haematopoietic origin. Rödeheffer and colleagues use lineage tracing to rule out that this is the case for white adipocytes, and show that they instead arise from CD24⁺ cells that are characterized by the expression of PdgfR (platelet-derived growth factor receptor).

Van den Brink and colleagues show that Nrf2, a regulator of the oxidative stress response, is required for several aspects of haematopoietic stem cell maintenance. Loss of Nrf2 results in the hyper-proliferation of haematopoietic stem and progenitor cells (HSPCs). Nrf2 is also required for HSPC migration and retention to their niche.

Oct4 cannot be replaced by other members of the same family of transcription factors to induce reprogramming. By comparing the structure of the POU family domain of Oct4 complexed to DNA with that of others, Schöler and colleagues identify an α-helix that is exposed on the surface of Oct4 and provides an interaction platform to recruit epigenetic modifiers to Oct4 targets. Mutations abolishing this helix suppress the reprogramming properties of Oct4.

Emery and colleagues show that during collective migration of Drosophila border cells, the Rab11 small GTPase regulates Rac activity throughout the cell cluster. They propose that Rab11 activates the actin-binding protein Moesin at the cell cortex, which allows the spatial restriction of Rac activity to the leading cell of the group.

Arlotta and Rouaux show that expression of the transcription factor Fezf2 in vivo is sufficient to redirect post-mitotic callosal projection neurons from one particular layer of the brain to corticofugal projection neurons that pertain to a different layer, including a redirection of their axonal connectivity.

Xenopus laevis and tropicalis tadpoles display incredible regenerative capacity of their tail. Amaya and colleagues find that tadpole tail amputation induces the production of reactive oxygen species (ROS) to induce cell proliferation and regeneration, through activation of the Wnt/β-catenin and Fgf20 signalling pathways.