Articles in 2013

How the characteristic quiescent status of adult HSCs is maintained is not well understood. Tenen and colleagues show that the transcription factor C/EBP is required to maintain a low proliferation rate in adult HSCs, partly through N-Myc repression.

Self-renewal and differentiation of adult stem cells ensures tissue homeostasis. De Haan and colleagues find that the chromatin-associated polycomb protein Cbx7 ensures self-renewal of haematopoietic stem cells (HSCs), whereas other polycomb proteins, such as Cbx8, induce differentiation. They find that although genes targeted by Cbx8 are highly expressed in HSCs and repressed in progenitors, Cbx7 target genes have the opposite expression pattern.

Watanabe and colleagues show that an increase in cytosolic G-actin levels following mechanical stress promotes Ca²⁺- and kinase-signalling-independent nucleation of actin filaments by formins.

The dynamic localization of PLK1 to kinetochores is required for faithful chromosome segregation. Peter, Sumara and colleagues demonstrate that a KHL22-containing E3 ligase mediates degradation-independent removal of PLK1 from kinetochores to ensure satisfaction of the spindle assembly checkpoint and proper mitotic progression.

Shen and colleagues find that initiation of prostate tumours by basal or luminal epithelial cells in mice leads to distinct tumour signatures. Interestingly, they find that although oncogenic transformation of basal cells gives rise to tumours with luminal phenotypes, tumours of luminal origins are more aggressive in functional tests and the distinct signature correlated with that of patients with aggressive tumours.

Tepass and colleagues use a series of mutant α-catenin forms to study the role of this protein in Drosophila in vivo. Their data support a model in which monomeric α-catenin links the cadherin–β-catenin complex at adherens junction to the actin cytoskeleton.

Wang and colleagues show that miR-126 and miR-126^* suppress metastasis by inhibiting the production of the Sdf-1α cytokine in mouse mammary tumours, resulting in decreased recruitment of mesenchymal stem cells and inflammatory monocytes to the tumour stroma.

Werb and colleagues demonstrate that GATA3, a transcription factor that promotes luminal differentiation in the mammary gland, suppresses breast cancer metastasis to the lung by upregulating miR-29b. This microRNA suppresses pro-metastatic characteristics, including mesenchymal traits and the expression of microenvironmental factors involved in angiogenesis and extracellular matrix remodelling.

In Drosophila neuroblasts, Centrobin marks the daughter centriole, which, in contrast to the mother centriole, is able to retain pericentriolar material (PCM) and organize an interphase microtubule aster thought to guide the subsequent asymmetric division. Gonzalez and colleagues demonstrate that Centrobin is necessary and sufficient to mediate this centrosome asymmetry, that it binds centriole and PCM proteins, and is regulated by POLO kinase.

The sprouting activity of filopodia emerging from endothelial sprouting cells needs to be compensated for in mature stable vessels. Adams and colleagues find that sprouting cells in mouse retinal vasculature show high VEGF uptake and VEGF receptor turnover, both essential for sprouting. These are inhibited by an aPKC-mediated decrease in VEGF receptor endocytosis in mature vessels, through a mechanism implicating clathrin-associated proteins, the transmembrane protein ephrin-B2 and the polarity factor PAR-3.

Gobel and colleagues show that the cortical protein ERM-1 drives expansion of the unicellular tube that constitutes the Caenorhabditis elegans excretory canal by recruiting membrane and cytoskeletal components, and the water channel aquaporin, to the apical side of the tube.

Labouesse and colleagues examine the steps of excretory canal growth in nematodes. They delineate the importance of osmoregulated vesicle fusion with the lumen, and of a subapical cytoskeletal web to ensure straight lumen growth. They identify PROS-1 as a transcription factor essential for lumen growth through modulation of the osmosensitive kinase GCK-3 and intermediate filament protein IFB-1.

Cortical actin is implicated in cell shape regulation during mitosis. Melchior and colleagues reveal that SCF^Fbxw5-mediated ubiquitylation and degradation of the actin remodeller Eps8 is required for timely cell rounding and progression into metaphase, whereas the capping activity of Eps8 is needed for mitotic exit.