Browse Articles

Endothelial cells undergo rearrangements during angiogenic sprouting. Gerhardt and colleagues show that the flux in Notch signalling levels in individual cells of sprouting vessels results in differential dynamics of VE-cadherin at junctions to drive functional endothelial cell rearrangements during sprouting. They also find that differential VE-cadherin dynamics are affected in retinopathy and tumour vessels.

Janes and colleagues use organotypic 3D models, transcriptomic analyses, mathematical modelling and in vivo tumour data to show that single cells oscillate between two anticorrelated expression states defined by TGFBR3 and JUND. They show that this signalling circuit is controlled by the engagement of the extracellular matrix, and propose that dynamic changes in gene expression states might underlie breast tumour heterogeneity.

Del Sal and colleagues demonstrate that the YAP and TAZ effectors of the Hippo pathway are under the control of the mevalonate pathway. They show that mutant p53 and SREBP-dependent activation of mevalonate signalling activates YAP and TAZ and promotes tumour formation in mice, a growth phenotype also conserved in Drosophila.

Vale and colleagues report the distinct abilities of different tubulin isotypes and post-translational modifications to regulate different microtubule motors and their properties.

Lecuit and colleagues use Drosophila embryo cellularization as an in vivo model system, as well as in vitro reconstitution assays, to show that septin mutant embryos display defects in actin organization and that septins are able to crosslink, bundle and bend actin filaments into rings.

Increased visceral adipose tissue has been associated with metabolic dysfunction but the origin of the progenitors that give rise to this tissue, and whether they are the same as the progenitors contributing to the protective subcutaneous adipose tissue, was unclear. Hastie and colleagues have found that Wt1-positive mesothelial cells contribute to visceral adipocytes.

Burridge and colleagues demonstrate that isolated nuclei respond to force by increasing their stiffness, and that this mechanical adaptation is mediated by emerin phosphorylation.

Defective asymmetric cell divisions of stem and progenitor cells are associated with tumorigenesis by a largely unknown mechanism. A signalling axis involving Snail, microRNA-146a and Numb is now shown to regulate the switch between symmetric and asymmetric cell division in colorectal cancer stem cells.

Collective cell migration depends on multicellular mechanocoupling between leader and follower cells to coordinate traction force and position change. Co-registration of Rho GTPase activity and forces in migrating epithelial cell sheets now shows how RhoA controls leader–follower cell hierarchy, multicellular cytoskeletal contractility and mechanocoupling, to prevent ectopic leading edges and to move the cell sheet forward.

Correct regulation of insulin secretion by the pancreas is crucial for organismal function and survival. The AMPK-related kinase SIK2 (salt-inducible kinase 2) is now shown to be stabilized in pancreatic β-cells following glucose stimulation, leading to improved systemic glucose homeostasis by regulating cellular calcium flux and insulin secretion.

In the second Review in our Genomic Instability series, Rudolph and colleagues discuss how the genomic damage that accumulates during ageing affects stem cell function through both cell-intrinsic and cell-extrinsic mechanisms.

Hebrok and colleagues use mouse models to demonstrate that loss of the chromatin modifier Brg1 cooperates with oncogenic KRas to form lesions resembling intraductal papillary mucinous neoplasia that progress to pancreatic adenocarcinoma.

Groth and colleagues identify proteins associated with newly synthesized DNA — isolated by nascent chromatin capture — as well as proteins associated with mature DNA, and find factors not previously linked to replication or nascent chromatin.

How sensory neurons integrate mechanical signals during touch sensation has remained unclear. Using a combination of laser axotomy and FRET imaging to measure force across single cells and molecules, Goodman and colleagues show that the neuronal spectrin cytoskeleton transduces touch sensation in C. elegans.

Silberzan and colleagues demonstrate that local RhoA activity and mechanical forces control the formation of 'migration fingers', cell protrusions involved in the leader-cell-driven collective migration of epithelial cell monolayers.

Screaton and colleagues delineate a pathway involving the AMPK-related Sik2 kinase using mouse models. They show that Sik2-mediated phosphorylation and subsequent degradation of CDK5R1 (p35) by PJA2 is needed for glucose-induced insulin secretion and β-cell functional compensation in models of hyperglycemia and obesity.