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The San Francisco Declaration on Research Assessment (DORA), an initiative spearheaded by the American Society for Cell Biology, aims to reform research assessment.
Defects in DNA replication, or in the pathways evolved to correct DNA replication problems, can cause genomic instability and disease. Zeman and Cimprich discuss recent advances in our understanding of the cellular responses to replication stress.
Stable RNA interference by shRNA provides a means to study multiple facets of gene function. Fellman and Lowe explore the rules of implementation of this silencing method in the vertebrate system for achieving maximal knockdown with minimal off-target effects.
Generation of differentiated kidney cell types from pluripotent stem cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. In three recent reports, mature kidney cell types and three-dimensional nephron-like structures were generated from pluripotent cells rapidly and efficiently. A detailed understanding of the signals that drive nephrogenesis proved critical for these achievements.
Signal integration is central to the regulation of patterning during plant development. During lateral root initiation, a signalling pathway controlled by the phloem-secreted TDIF peptide is found to activate the auxin signalling pathway independently of auxin, through phosphorylation of ARF transcription factors by GSK3 (Shaggy-like) kinases.
Macroautophagy is a key regulator of cellular integrity and viability, but how the process facilitates apoptosis has remained poorly defined. It has now become clear that autophagy degrades the Fap-1 protein phosphatase, a critical negative regulator of apoptotic cell death signalled by the TNF receptor family member, Fas.
To delineate the characteristics of lineage emergence in the early mammalian embryo, Hiiragi and colleagues analyse the expression profiles of single cells of the inner cell mass as they differentiate into pluripotent epiblast and primitive endoderm. They observe that cells with initially indistinguishable expression profiles, but exhibiting apparently stochastic differences, resolve into distinct lineages in the late blastocyst through the action of Fgf4.
In bacteria, the tubulin-related GTPase FtsZ and the actin-related protein FtsA cooperate to form the Z-ring required for cytokinesis. Loose and Mitchison now show that FtsZ and FtsA can self-organize into dynamic structures in vitro, providing insights into the potential regulatory interplay of the two proteins.
Data suggest that autophagy, a process normally associated with cell survival, also promotes cell death, depending on the stimulus or cell type. Thorburn and colleagues find that differences in basal autophagy levels in cells determine survival or death in response to death receptor activation, through modulation of Fap-1 degradation.
Liu and colleagues find that MLKL translocates to the plasma membrane to induce TNF-induced necroptosis, possibly through an effect on calcium influx and the action of the cation channel TRPM7.
Auxin signalling controls events in plant development, but it is unclear how auxin sensitivity is regulated. Hwang and colleagues find that phosphorylation of AUXIN RESPONSE FACTORS (ARFs) by BRASSINOSTEROID-INSENSITIVE 2 (BIN2) suppresses their interaction with the repressors AUX/IAA to enhance the transcription of auxin target genes, which is essential for lateral root emergence.
How misfolded proteins are extracted from the endoplasmic reticulum (ER) for degradation remains unclear. Sommer and colleagues demonstrate that following assembly into the HRD ligase complex, Der1 forms oligomers in the ER membrane and enables extraction of proteins from the ER lumen.
Rab GTPases are important mediators of vesicle trafficking, but how they are regulated is not clear. Thompson and colleagues find that calcium efflux through the ion channel P2XA in the Dictyostelium discoideum contractile vacuole leads to activation of the Rab GTPase-activating protein CnrF, which in turn inactivates Rab11a to allow vacuole fusion.
Lowry and colleagues report the potential role of stem cell quiescence as a tumour suppressive mechanism. They show that although hair follicle stem cell activation allows tumour formation in response to oncogenic stimuli, tumours are not initiated during the quiescent phase of the hair cycle. They further find that the presence of Pten is important in maintaining hair follicle stem cell quiescence in this setting.
Camargo and colleagues employed an RNAi screen to identify LKB1 as an upstream regulator of the Hippo pathway. They show that LKB1 regulates SCRIB localization through the MARK kinase, leading to regulation of the activity of YAP through MST1/2 kinases.
Differentiation of pluripotent cells into renal lineages has had limited success so far. Melissa Little and colleagues have used defined medium conditions that induce posterior primitive streak and intermediate mesoderm using growth factors used during normal embryogenesis. This results in the synchronous induction of both components of the kidney, the ureteric bud and metanephric mesenchyme, which form a self-organizing nephron structure in vitro.
