Reviews & Analysis

Stem cells, and the microenvironment or 'niche' that influences them, must often reside in a particular location within a tissue to perform their function. Integrin-mediated adhesion is now shown to regulate the location of the stem-cell niche in the Drosophila testis.

Collective cell invasion into the extracellular matrix (ECM) has been observed in malignant tumours and in tissue morphogenesis. To achieve this, leading cells trigger both proteolytic and structural modifications of the ECM to create channels that precede progressively widening chains of following cells.

How is RNA Polymerase II (RNAP) regulated at poised loci in embryonic stem cells? Recent work provides new insights into Ring1-mediated transcriptional control of this important subset of developmental regulatory genes.

The control of cell size through the coordination of cell growth and division is a longstanding fundamental problem. A study in fission yeast shows that TOR controls entry into mitosis through the MAP kinase Sty1 and so provides a molecular mechanism for the control of cell size.

Most intracellular organelles are surrounded by a lipid bilayer and require specialized machinery for membrane fusion. Remarkably, lipid droplets, which contain a hydrophobic core and a monolayer of membrane lipids, can sequester distinct components of this fusion machinery and thereby downregulate certain types of exocytosis.

The mitotic spindle is the molecular machine that distributes the chromosomes to the two daughter cells. By developing techniques to look at the behaviour of individual microtubules within the spindle, new insights into the organization of this exquisite structure have been provided.

How do developing organs sense and limit their size? The recently discovered Hippo pathway might have a critical role in controlling organ size and homeostasis in many organisms from Drosophila to mammals.

Mitochondrial dysfunction is primarily responsible for neurodegeneration in Parkinson's disease. The Parkinson's-disease-associated kinase PINK1 has been identified as an important regulator of the activity of the mitochondria-associated stress-protective protease HtrA2.

The transcription factor PPAR-γ determines whether mesenchymal stem cells differentiate into adipocytes or osteoblasts. The finding that non-canonical Wnt signalling represses PPAR-γ through assembly of a nuclear corepressor complex containing the histone methyltransferase SETDB1 provides the first insight into how extracellular signals can regulate chromatin modification.

Mitosis in vertebrates involves nuclear-envelope breakdown and dispersal. On completion of chromatid segregation, disassembled nuclear-envelope components are reused to form nuclear membranes in the two daughter cells, and the endoplasmic reticulum membrane seems to make a key contribution to this process.

The class III phosphatidylinositol 3-kinase (PI(3)KC3) is part of a key complex regulating autophagy. How this complex mechanistically contributes to autophagosome formation remains largely unknown. The BAR-domain-containing protein Bif-1/endophilin B1, commonly associated with the control of membrane curvature, has been identified as a new interacting partner for PI(3)KC3, suggesting the complex plays an active part in the regulation of membrane dynamics during autophagy.

The transcription factor Hand1 is required for cell-fate determination during placental development. Recent work shows that release of Hand1 from the nucleolus controls differentiation of trophoblast stem cells into trophoblast giant cells, and this switch is controlled by the antagonistic activities of HICp40 and Polo-like kinase-4 (Plk4).

The evolutionarily conserved PAR3–PAR6–aPKC–Cdc42 complex has a well-established role in cell polarity. The exact job of PAR proteins in polarity is not known, but the finding that they affect endocytosis casts new light on their function.

Toll-like receptors participate in the inflammatory response and are now shown to act in neural precursor cells to regulate adult hippocampal neurogenesis. The dialogue between inflammatory components and neural precursor cells might have important consequences for central nervous system homeostasis and repair.

Most organisms, from bacteria to humans, can follow temperature gradients to an optimal temperature. Experience influences eukaryotes' preferred temperature, and, as it turns out, bacteria also adjust their temperature preference depending on growth conditions.

During development, stem and progenitor cells gradually commit to differentiation pathways. Cell fate decisions are regulated by differentiation factors, which activate transcription programmes that specify lineage and differentiation status. Among these factors, the transforming growth factor (TGF)-β family is important in both lineage selection and progression of differentiation of most, if not all, cell and tissue types. There is now increasing evidence that TGF-β family proteins have the ability to redirect the differentiation of cells that either have fully differentiated or have engaged in differentiation along a particular lineage, and can thereby elicit 'transdifferentiation'. This capacity for cellular plasticity is critical for normal embryonic development, but when recapitulated in the adult it can give rise to, or contribute to, a variety of diseases. This is illustrated by the ability of TGF-β family members to redirect epithelial cells into mesenchymal differentiation and to cause switching of mesenchymal cells from one lineage to another. Hence, various pathologies in adults may be considered diseases of abnormal development and differentiation.