Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming.

Lower vertebrate and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through the reprogramming of pre-existing cardiomyocytes. However, how cardiac injury initiates signaling pathways controlling this regenerative reprogramming remains to be defined. Here, we utilize in vivo biophysical and genetic fate mapping zebrafish studies to reveal that altered hemodynamic forces due to cardiac injury activate a sequential endocardial-myocardial signaling cascade to direct cardiomyocyte reprogramming and heart regeneration.

Correction to: Mitochondrial H-ATP synthase in human skeletal muscle: contribution to dyslipidaemia and insulin resistance.

Owing to an oversight, the authors omitted to note that Dr Taub is a co-founder of and equity holder in Cardero Therapeutics.

Mitochondrial H-ATP synthase in human skeletal muscle: contribution to dyslipidaemia and insulin resistance.

Aims/hypothesis: Mitochondria are important regulators of the metabolic phenotype in type 2 diabetes. A key factor in mitochondrial physiology is the H-ATP synthase. The expression and activity of its physiological inhibitor, ATPase inhibitory factor 1 (IF1), controls tissue homeostasis, metabolic reprogramming and signalling.

PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position.

Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancer-promoting phosphatase PRL-3 (PTP4A3), which is overexpressed in several epithelial cancers, in polarized epithelial MDCK and Caco2 cells leads to invasion and the formation of multiple ectopic, fully polarized lumens in cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer.

Myocardial plasticity: cardiac development, regeneration and disease.

The adult mammalian heart is unable to recover from myocardial cell loss due to cardiac ischemia and infarction because terminally differentiated cardiomyocytes proliferate at a low rate. However, cardiomyocytes in other vertebrate animal models such as zebrafish, axolotls, newts and mammalian mouse neonates are capable of de-differentiating in order to promote cardiomyocyte proliferation and subsequent cardiac regeneration after injury. Although de-differentiation may occur in adult mammalian cardiomyocytes, it is typically associated with diseased hearts and pathologic remodeling rather than repair and regeneration.

EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis.

Establishing the correct orientation of the mitotic spindle is an essential step in epithelial cell division in order to ensure that epithelial tubules form correctly during organ development and regeneration. While recent findings have identified some of the molecular mechanisms that underlie spindle orientation, many aspects of this process remain poorly understood. Here, we have used the 3D-MDCK model system to demonstrate a key role for a newly identified protein complex formed by IQGAP1 and the epithelial growth factor receptor (EGFR) in controlling the orientation of the mitotic spindle.

KIF16B delivers for transcytosis.

EMBO J 32 15, 2125–2139 doi:; DOI: 10.1038/emboj.2013.

Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells.

The formation of epithelial tissues requires both the generation of apical-basal polarity and the coordination of this polarity between neighbouring cells to form a central lumen. During de novo lumen formation, vectorial membrane transport contributes to the formation of a singular apical membrane, resulting in the contribution of each cell to only a single lumen. Here, from a functional screen for genes required for three-dimensional epithelial architecture, we identify key roles for synaptotagmin-like proteins 2-a and 4-a (Slp2-a/4-a) in the generation of a single apical surface per cell.

Divide and polarize: recent advances in the molecular mechanism regulating epithelial tubulogenesis.

Epithelial organs are generated from groups of non-polarized cells by a combination of processes that induce the acquisition of cell polarity, lumen formation, and the subsequent steps required for tubulogenesis. The subcellular mechanisms associated to these processes are still poorly understood. The extracellular environment provides a cue for the initial polarization, while cytoskeletal rearrangements build up the three-dimensional architecture that supports the central lumen.