The PECAn image and statistical analysis pipeline identifies Minute cell competition genes and features.

Investigating organ biology often requires methodologies to induce genetically distinct clones within a living tissue. However, the 3D nature of clones makes sample image analysis challenging and slow, limiting the amount of information that can be extracted manually. Here we develop PECAn, a pipeline for image processing and statistical data analysis of complex multi-genotype 3D images. PECAn includes data handling, machine-learning-enabled segmentation, multivariant statistical analysis, and graph generation. This enables researchers to perform rigorous analyses rapidly and at scale, without requiring programming skills. We demonstrate the power of this pipeline by applying it to the study of Minute cell competition. We find an unappreciated sexual dimorphism in Minute cell growth in competing wing discs and identify, by statistical regression analysis, tissue parameters that model and correlate with competitive death. Furthermore, using PECAn, we identify several genes with a role in cell competition by conducting an RNAi-based screen.

In search of conserved principles of planar cell polarization.

The making of an embryo and its internal organs entails the spatial coordination of cellular activities. This manifests during tissue morphogenesis as cells change shape, rearrange and divide along preferential axis and during cell differentiation. Cells live in a polarized field and respond to it by polarizing their cellular activities in the plane of the tissue by a phenomenon called planar cell polarization. This phenomenon is ubiquitous in animals and depends on a few conserved planar cell polarity (PCP) pathways. All PCP pathways share two essential characteristics: the existence of local interactions between protein complexes present at the cell surface leading to their asymmetric distribution within cells; a supracellular graded cue that aligns these cellular asymmetries at the tissue level. Here, we discuss the potential common principles of planar cell polarization by comparing the local and global mechanisms employed by the different PCP pathways identified so far. The focus of the review is on the logic of the system rather than the molecules per se.

Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry.

Interfaces between cells with distinct genetic identities elicit signals to organize local cell behaviors driving tissue morphogenesis. The Drosophila embryonic axis extension requires planar polarized enrichment of myosin-II powering oriented cell intercalations. Myosin-II levels are quantitatively controlled by GPCR signaling, whereas myosin-II polarity requires patterned expression of several Toll receptors. How Toll receptors polarize myosin-II and how this involves GPCRs remain unknown. Here, we report that differential expression of a single Toll receptor, Toll-8, polarizes myosin-II through binding to the adhesion GPCR Cirl/latrophilin. Asymmetric expression of Cirl is sufficient to enrich myosin-II, and Cirl localization is asymmetric at Toll-8 expression boundaries. Exploring the process dynamically, we reveal that Toll-8 and Cirl exhibit mutually dependent planar polarity in response to quantitative differences in Toll-8 expression between neighboring cells. Collectively, we propose that the cell surface protein complex Toll-8/Cirl self-organizes to generate local asymmetric interfaces essential for planar polarization of contractility.

Fat2 and Lar Dance a Pas de Deux during Collective Cell Migration.

What coordinates the internal leading and trailing edges in collectively migrating cells is largely unknown. In this issue of Developmental Cell, Barlan et al. (2017) delineate a Fat2/Lar planar signaling pathway at the basal, motile cell-cell contacts of Drosophila egg chamber follicle cells.