Orienting the Direction of EGFR Activation

Morphogens are typically distributed symmetrically from their source of production. In this issue of Developmental Cell, Peng et al. (2012) demonstrate that a bias in the directionality of protrusions emanating from cells secreting the EGFR ligand Spitz leads to asymmetric activation of the pathway

Pre-Steady-State Decoding of the Bicoid Morphogen Gradient

Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may precede the convergence of the gradient to its steady state. Here we consider the implications of pre-steady-state decoding of the Bicoid morphogen gradient for patterning of the anterior–posterior axis of the Drosophila embryo. Quantitative analysis of the shift in the expression domains of several Bicoid targets (gap genes) upon alteration of bcd dosage, as well as a temporal analysis of a reporter for Bicoid activity, suggest that a transient decoding mechanism is employed in this setting. We show that decoding the pre-steady-state morphogen profile can reduce patterning errors caused by fluctuations in the rate of morphogen production. This can explain the surprisingly small shifts in gap and pair-rule gene expression domains observed in response to alterations in bcd dosage

N-WASP Is Required for Structural Integrity of the Blood-Testis Barrier

During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation

Polarized Secretion of Drosophila EGFR Ligand from Photoreceptor Neurons Is Controlled by ER Localization of the Ligand-Processing Machinery

Trafficking within the endoplasmic reticulum and specialized localization of the intra-membrane protease Rhomboid regulate EGF ligand-dependent signaling in Drosophila photoreceptor axon termini

Identifying and predicting social lifestyles in people’s trajectories by neural networks

Abstract In this research, we exploit repeated parts in daily trajectories in people’s movements, which we refer to as mobility patterns, to train models to identify and predict a person’s lifestyles. We use cellular data of a group (“society”) of people and represent a person’s daily trajectory using semantic labels (e.g., “home”, “work”, and “gym”) given to the main places of interest (POI) he has visited during the day, as determined collectively based on interviewing all people of the group. First, in an unsupervised manner using a neural network (NN), we embed POI-based daily trajectories that always appear together with others in consecutive weeks and identify the result of this embedding with social lifestyles. Second, using these lifestyles as labels for lifestyle prediction, user POI-based daily trajectories are used to train a convolutional NN to extract mobility patterns in the trajectories and a dynamic NN with flexible memory to assemble these patterns to predict a lifestyle for a trajectory never-seen-before. The two-stage algorithm shows model accuracy and generalizability in lifestyle identification and prediction (both for a novel trajectory and a novel user) that are superior to those shown by state-of-the-art algorithms. The code for the algorithm and data sets used in our experiments are available online

The Edges of Pancreatic Islet β Cells Constitute Adhesive and Signaling Microdomains

Pancreatic islet β cells are organized in rosette-like structures around blood vessels and exhibit an artery-to-vein orientation, but they do not display the typical epithelial polarity. It is unclear whether these cells present a functional asymmetry related to their spatial organization. Here, we identify murine β cell edges, the sites at which adjacent cell faces meet at a sharp angle, as surface microdomains of cell-cell adhesion and signaling. The edges are marked by enrichment of F-actin and E-cadherin and are aligned between neighboring cells. The edge organization is E-cadherin contact dependent and correlates with insulin secretion capacity. Edges display elevated levels of glucose transporters and SNAP25 and extend numerous F-actin-rich filopodia. A similar β cell edge organization was observed in human islets. When stimulated, β cell edges exhibit high calcium levels. In view of the functional importance of intra-islet communication, the spatial architecture of their edges may prove fundamental for coordinating physiological insulin secretion