Articles in 2013

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.

The oocyte environment is critical for its development. Conti and colleagues demonstrate that, in mouse, amphiregulin-stimulated somatic cumulus cells promote translation of maternal mRNAs in the oocyte in a manner dependent on oocyte PI(3)K signalling.

It has been unclear how round cells elongate during mouse embryo compaction. Plachta and colleagues use live imaging to demonstrate that E-cadherin-dependent filopodia extend to neighbouring cells to drive elongation and compaction.

Cancer is associated with altered DNA methylation. Using whole-genome single-nucleotide sequencing, Adams and colleagues reveal that senescent cells, as well as cells that have bypassed senescence through p53 and pRB inactivation, exhibit methylation changes similar to those seen in cancer.

The stability of the PTEN tumour suppressor protein is regulated by polyubiquitylation. Ma and colleagues identify USP13 as an enzyme reversing polyubiquitylation of PTEN, leading to PTEN stabilization and tumour suppression.

How centrioles are amplified to produce multicilia is unclear, but a structure named the deuterosome has been implicated in the process. Zhu and colleagues demonstrate that Deup1, a paralogue to the centriole protein Cep63, governs deuterosome formation and mediates large-scale de novo centriole amplification in multiciliated cells.

Zon and colleagues have performed a reverse genetic screen to target orthologues of 425 human chromatin factors in zebrafish. This allowed them to delineate chromatin regulators that function at distinct stages of primitive and definitive blood formation.

Differentiation of pluripotent cells into renal lineages has so far demonstrated limited success. Juan Carlos Ispizua Belmonte and colleagues have used defined medium conditions to obtain committed renal progenitor cells that are able to integrate into a ureteric bud in a three-dimensional culture system.

Obesity results from accumulation of white adipose tissue, whereas brown adipose tissue can counteract these effects through thermogenesis. Ning and colleagues have found that the GPCR family member Lgr4 controls the balance between brown and white adipose tissue. In its absence, mice have reduced adiposity and obesity symptoms, and exhibit an increase in brown-like adipocytes, possibly the result of a decrease in Rb expression.

Terman and colleagues employed a genetic screen in Drosophila to identify the SelR methionine sulfoxide reductase as the enzyme responsible for reversing the Mical-mediated oxidation of actin. Thus, SelR antagonizes the effects of Semaphorin–Plexin–Mical-dependent signalling in vivo.

As epithelial tissue spreads during development and wound healing, epithelial integrity needs to be maintained. Heisenberg and colleagues show that tension modulates cell division orientations during zebrafish epiboly through cell elongation and control of myosin II activity to prevent cell fusion and epithelial disruption.

Until the recent discovery of the mitochondrial calcium uniporter (MCU), the effect of increases in mitochondrial calcium levels could not be tested in vivo. Finkel and colleagues have knocked out the gene coding for MCU in adult mice, and show that MCU is required for transport of calcium into the mitochondria. They also show that, in its absence, the function of skeletal muscle is altered; however, surprisingly, no effects are observed on the sensitivity to cell-death-inducing agents.

Error-free genome segregation depends on the spindle assembly checkpoint (SAC), a signalling network that delays anaphase onset until chromosomes have established proper spindle attachments. Three reports now quantitatively examine the sensitivity and robustness of the SAC response.

In vivo time-lapse imaging and functional tests bring fresh evidence that the morphogen Hedgehog is conveyed to target cells via long filopodia extensions, dubbed cytonemes. This study provides the tools and conceptual framework to understand how cytonemes form and carry morphogens.

The mTOR protein kinase controls anabolic processes as part of mTOR complexes 1 and 2 (mTORC1 and mTORC2). The two complexes are now shown to be involved in a negative feedback regulatory mechanism, in which mTORC1 stimulation inactivates mTORC2 through the inhibitory phosphorylation of the mTORC2 component Sin1.

In an insertional mutagenesis screen, Sabatini and colleagues identify the small G protein ARF4 as a mediator of cell death in response to brefeldin A (BFA) treatment. BFA-induced Golgi stress upregulates ARF4, and loss of ARF protects against propagation of pathogens known to induce Golgi fragmentation.

Aguirre-Ghiso and colleagues report that the intensity of TGF-β2 signalling dictates dormancy or metastatic growth of disseminated tumour cells by regulating the activity of p38α/β in different target organs.

Schiebel and colleagues use in vitro techniques and yeast genetics to study the role of GTP binding in the microtubule nucleation activity of γ-tubulin.

Wei and colleagues report that phosphorylation of Sin1 by S6K or Akt results in its dissociation from mTORC2, thus suppressing mTORC2 activity. A cancer-patient-derived Sin1 mutation that impairs this phosphorylation leads to mTORC2 hyperactivation and increased tumour formation in mice.

During vertebrate embryogenesis, the pharyngeal arch arteries (PAA) connect segments of the primitive circulation. Burns and colleagues show that Nkx2.5⁺ heart precursors from the lateral plate mesoderm surprisingly give rise to the PAA angioblasts, and that Nkx2.5 is required for PAA development.