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Despite being one of the most studied signalling pathways, precisely how phospholipid synthesis is regulated in the phosphoinositide signalling cascade remains unclear. The scaffold protein IQGAP1 is now shown to orchestrate the assembly of a multi-enzyme complex that streamlines PtdIns(3,4,5)P3 synthesis to facilitate Akt activation in response to extracellular stimuli.
Many cell types in our body move in a collective manner, which requires individual cells to align their movements relative to that of their neighbours. A mechanism is now described in which cadherin-rich protrusions are extended from leading migrating cells and engulfed by follower cells to guide collective migration.
Work from the early 1980s reported strange lobes protruding from Caenorhabditis elegans germ cell precursors. However, the fate and potential significance of these lobes remained unexplored for decades. Now, neighbouring endodermal cells are shown to sever and digest these lobes, in an unexpected process of 'intercellular cannibalism', which could play an important part in regulating primordial germ cells.
Kaminski et al. demonstrate that combined expression of the transcription factors Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells.
Ramkumar et al. demonstrate that Crumbs2 is required in the cells of the primitive streak to promote cell ingression during the epithelial-to-mesenchymal transition, and maintains the integrity of the epiblast.
Costa et al. show that asymmetric positioning of the mitotic spindle during endothelial tip cell divisions produces daughter cells of different sizes and the ensuing asymmetry of Vegfr distribution drives Notch-independent tip/stalk cell selection.
Caenorhabditis elegans primordial germ cells (PGCs) transiently extend large lobes, which are found to be actively removed and digested by endodermal cells to alter PGC content in a process dependent on actin and dynamin.
Hayer et al. observe that collectively migrating endothelial cells extend rear VE-cadherin-rich membrane structures that are engulfed by follower cells, correlating spatially with the direction of movement.
Anderson et al. show that IQ-motif-containing GTPase-activating protein 1 (IQGAP1) acts as a scaffold for the phosphoinositide kinases that mediate the sequential phosphorylation of phosphoinositides to generate PtdIns(3,4,5)P3 and downstream signalling.
Weaver and colleagues report that enrichment of the extracellular matrix with tenascin C promotes aggressiveness of IDH1-mutant glioblastoma by activating a HIF1α-controlled mechanosignalling feedback loop.
Blaas et al. traced Lgr6+ cells during mammary gland formation, homeostasis, pregnancy and tumorigenesis, and found that they represent a population of unipotent progenitors that contribute to alveologenesis and can initiate luminal mammary tumours.
Hansen et al. find that SCAI (suppressor of cancer cell invasion) is a 53BP1-binding protein that acts to repair in heterochromatin and to facilitate meiotic recombination in germ cells.