Reviews & Analysis

During development, embryonic cells sculpt three-dimensional tissues. Although cell polarity is commonly analysed along one, and sometimes two, dimensions, this perspective illustrates how higher-order cell polarity regulates convergent extension — the coordinated cell rearrangement that produces solid tissue elongation.

The Hedgehog (Hh) pathway plays central roles in animal development and stem-cell function. Defects in Hh signalling lead to birth defects and cancer in humans. The first and often genetically damaged step in this pathway is the interaction between two membrane proteins — Patched (Ptc), encoded by a tumour suppressor gene, and Smoothened (Smo), encoded by a proto-oncogene. Recent work linking Hh signalling to sterol metabolites and protein-trafficking events at the primary cilium promises to shed light on the biochemical basis of how Patched inhibits Smoothened, and to provide new avenues for cancer treatment.

A new study of the zebrafish intestine has uncovered a transcriptional hierarchy controlling lumen formation and proposes a model for how transcellular and paracellular transport synergize to ensure that only a single lumen is produced.

Last year it was reported that a cocktail of four transcription factors — encoded by Oct4, Sox2, Myc and Klf4 — can partly reprogramme mouse somatic cells to an embryonic state, a process that reawakens silenced segments of the genome and restores pluripotency to the somatic cell nucleus. Three groups have now modified this method to generate fully reprogrammed cells that closely resemble embryonic stem cells.

Permeabilization of the mitochondria usually leads to caspase activation and apoptosis. In the absence of caspase activation, these same mitochondrial changes can also lead to cell death. A recent study suggests that when good mitochondria go bad, the activation of both glycolysis and autophagy may permit cellular survival.

PIM protein kinases have been known for some time as oncogenes that promote lymphomagenesis together with MYC (c-Myc). It is now reported that PIM1 is a coactivator of MYC, and it phosphorylates serine 10 of histone H3 at MYC target genes. These results may shed new mechanistic light on how PIM1 cooperates with MYC in tumorigenesis.

Membrane microdomains are widely postulated to regulate cell signalling, especially at the plasma membrane. Despite intense study, how this occurs remains largely unknown. New work now suggests that for MAP (mitogen-activated protein) kinase signalling, microdomains containing Ras nanoclusters contribute to the fidelity of signal transduction by acting as digital switches.

The molecular mechanisms through which the epidermal growth factor receptor (EGFR) promotes normal cell migration and carcinoma invasion are incompletely understood. A new study reveals that EGFR induces a switch in expression from tensin to its endogenous inhibitor cten (C-terminal tensin-like protein), alleviating integrin linkage to the cytoskeleton. Analysis of clinical samples suggests that this may be important for breast cancer invasion.

As legends go, when Alexander the Great crossed the Land of Darkness searching for the elixir of life, he encountered only desert. Thousands of years later, is it too optimistic to think that scientists have finally found the secret to a longer life? A recent study suggests that p63 may be key, at least for many epithelial stem cells.

Degradation of the MYC oncoprotein through site-specific phosphorylation and recognition by the ubiquitin ligase Fbw7 is central for controlling cell growth and tumorigenesis. New work adds another layer of complexity by showing that the deubiquitinating enzyme Usp28 'piggybacks' on the nuclear isoform of the ligase and stabilizes MYC, thus explaining the selective degradation of MYC in the nucleolus.

Bacterial protein secretion is an important process necessary for adhesion, motility, communication, nutrient acquisition, and virulence. Secretion is energy intensive and time sensitive, so it needs to be tightly regulated. Recent work indicates that threonine phosphorylation can provide this control.

Two recent studies in Drosophila demonstrate that overexpression of proteins required for centriole duplication can not only induce centriole over-duplication in cells containing centrioles, but can also drive de novo centriole assembly in unfertilized eggs that initially lack centrioles. These studies offer a new perspective on the mechanisms that control centriole duplication.

Specification of the axon and dendrites is a critical step in the development of a neuron and requires the asymmetric organization of the cell. A possible link between the extrinsic and intrinsic pathways that drive axon specification has been made with the finding that Dishevelled acts downstream of Wnt5a to activate the PAR6–aPKC–PAR3 pathway.

Exciting new work identifies phospholipase D2 (PLD2) as an unexpected player upstream of Ras activation in epidermal growth factor (EGF)- and T-cell receptor-regulated signalling pathways. Phosphatidic acid (PA) generated on the plasma membrane by activated PLD2 directly recruits the guanine nucleotide-exchange factor Sos, or after conversion to diacylglycerol (DAG), recruits RasGRP1. These results demand a rewiring of some well-established circuit diagrams.

Small open-reading frames are difficult to detect both computationally and by mutagenesis. An mRNA previously thought to be non-coding has now been found to produce four tiny peptides that function non-cell autonomously to organize epithelial actin during Drosophila development.

Caspases are proteases that regulate apoptosis as well as inflammation. Denecker et al. show that caspase-14 controls the maturation of the epidermis by proteolytically processing filaggrin. The ultimate products of this cleavage prevent UVB photodamage and water loss, affecting skin osmolarity and moisture. Although this work sets caspase-14 apart from its family members, it also reinforces their role in host defence responses.

In the cell, microtubule organizing centers (MTOCs) dynamically nucleate microtubules and arrange them in functional patterns, but microtubule anchoring to MTOCs is not well understood. A novel fission-yeast protein that anchors the γ-tubulin-containing nucleating complex (γ-TuC) at the spindle pole during mitosis has now been described. The work highlights the complex regulation of microtubule anchoring.