Volume 15 Issue 2, February 2013

Cédric Blanpain discusses the progress achieved in identifying and characterizing the cellular origins of different solid tumours in mouse models of skin, brain, breast, gut and lung cancer, using genetic lineage tracing approaches.

The endoplasmic reticulum (ER) is a heterogeneous organelle with distinct morphologies of sheets and an interconnected network of tubules sharing a common lumen. An ER domain marked by the Rab10 GTPase and several lipid-synthesizing enzymes is implicated in dynamic ER tubule formation and fusion events in cells.

Most organs are composed of tubes of differing cellular architectures, including intracellular 'seamless' tubes. Two studies examining the morphogenesis of the seamless tubes formed by the excretory canal cell in Caenorhabditis elegans reveal a previously unappreciated role for osmoregulation of tubulogenesis: hyperosmotic shock recruits canalicular vesicles to the lumenal membrane to promote seamless tube growth.

Tumour cells are influenced by their microenvironment, which can promote uncontrolled growth, invasion and metastasis. The GATA3 transcription factor is now shown to regulate the tumour microenvironment by inducing the expression of miR-29b in cancer cells. This microRNA in turn inhibits the expression of genes involved in angiogenesis and extracellular matrix signalling and remodelling to suppress metastasis.

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.

ER tubules grow and fuse to give the ER its characteristic shape. English and Voeltz show that the small GTPase Rab10 is crucial for ER tubule growth and fusion. Rab10 localizes to the leading edge of new ER tubules with enzymes that promote phospholipid synthesis, suggesting that ER tubule growth, fusion and phospholipid synthesis might be coupled.

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.

Muthuswamy and colleagues demonstrated that loss of the Par3 polarity protein cooperates with ErbB2 activity to promote cell invasion and metastasis by destabilizing E-cadherin-dependent cell–cell junctions.

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.

Arlotta and Rouaux show that expression of the transcription factor Fezf2 in vivo is sufficient to redirect post-mitotic callosal projection neurons from one particular layer of the brain to corticofugal projection neurons that pertain to a different layer, including a redirection of their axonal connectivity.

Xenopus laevis and tropicalis tadpoles display incredible regenerative capacity of their tail. Amaya and colleagues find that tadpole tail amputation induces the production of reactive oxygen species (ROS) to induce cell proliferation and regeneration, through activation of the Wnt/β-catenin and Fgf20 signalling pathways.