Versatile system cores as a conceptual basis for generality in cell and developmental biology.

The discovery of general principles underlying the complexity and diversity of cellular and developmental systems is a central and long-standing aim of biology. While new technologies collect data at an ever-accelerating rate, there is growing concern that conceptual progress is not keeping pace. We contend that this is due to a paucity of conceptual frameworks that support meaningful generalizations.

Competence for neural crest induction is controlled by hydrostatic pressure through Yap.

Embryonic induction is a key mechanism in development that corresponds to an interaction between a signalling and a responding tissue, causing a change in the direction of differentiation by the responding tissue. Considerable progress has been achieved in identifying inductive signals, yet how tissues control their responsiveness to these signals, known as competence, remains poorly understood. While the role of molecular signals in competence has been studied, how tissue mechanics influence competence remains unexplored.

Segregated cation flux by TPC2 biases Ca signaling through lysosomes.

Two-pore channels are endo-lysosomal cation channels with malleable selectivity filters that drive endocytic ion flux and membrane traffic. Here we show that TPC2 can differentially regulate its cation permeability when co-activated by its endogenous ligands, NAADP and PI(3,5)P. Whereas NAADP rendered the channel Ca-permeable and PI(3,5)P rendered the channel Na-selective, a combination of the two increased Ca but not Na flux.

Self-organized collective cell behaviors as design principles for synthetic developmental biology.

Over the past two decades, molecular cell biology has graduated from a mostly analytic science to one with substantial synthetic capability. This success is built on a deep understanding of the structure and function of biomolecules and molecular mechanisms. For synthetic biology to achieve similar success at the scale of tissues and organs, an equally deep understanding of the principles of development is required.

Desensitisation of Notch signalling through dynamic adaptation in the nucleus.

During embryonic development, signalling pathways orchestrate organogenesis by controlling tissue-specific gene expression programmes and differentiation. Although the molecular components of many common developmental signalling systems are known, our current understanding of how signalling inputs are translated into gene expression outputs in real-time is limited. Here we employ optogenetics to control the activation of Notch signalling during Drosophila embryogenesis with minute accuracy and follow target gene expression by quantitative live imaging.

An image-based data-driven analysis of cellular architecture in a developing tissue.

Quantitative microscopy is becoming increasingly crucial in efforts to disentangle the complexity of organogenesis, yet adoption of the potent new toolbox provided by modern data science has been slow, primarily because it is often not directly applicable to developmental imaging data. We tackle this issue with a newly developed algorithm that uses point cloud-based morphometry to unpack the rich information encoded in 3D image data into a straightforward numerical representation. This enabled us to employ data science tools, including machine learning, to analyze and integrate cell morphology, intracellular organization, gene expression and annotated contextual knowledge.

Using optogenetics to tackle systems-level questions of multicellular morphogenesis.

Morphogenesis of multicellular systems is governed by precise spatiotemporal regulation of biochemical reactions and mechanical forces which together with environmental conditions determine the development of complex organisms. Current efforts in the field aim at decoding the system-level principles underlying the regulation of developmental processes. Toward this goal, optogenetics, the science of regulation of protein function with light, is emerging as a powerful new tool to quantitatively perturb protein function in vivo with unprecedented precision in space and time.

Dynamic Buffering of Extracellular Chemokine by a Dedicated Scavenger Pathway Enables Robust Adaptation during Directed Tissue Migration.

How tissues migrate robustly through changing guidance landscapes is poorly understood. Here, quantitative imaging is combined with inducible perturbation experiments to investigate the mechanisms that ensure robust tissue migration in vivo. We show that tissues exposed to acute "chemokine floods" halt transiently before they perfectly adapt, i.

Principles and applications of optogenetics in developmental biology.

The development of multicellular organisms is controlled by highly dynamic molecular and cellular processes organized in spatially restricted patterns. Recent advances in optogenetics are allowing protein function to be controlled with the precision of a pulse of laser light , providing a powerful new tool to perturb developmental processes at a wide range of spatiotemporal scales. In this Primer, we describe the most commonly used optogenetic tools, their application in developmental biology and in the nascent field of synthetic morphogenesis.

Clearance by Microglia Depends on Packaging of Phagosomes into a Unique Cellular Compartment.

Phagocytic immune cells such as microglia can engulf and process pathogens and dying cells with high efficiency while still maintaining their dynamic behavior and morphology. Effective intracellular processing of ingested cells is likely to be crucial for microglial function, but the underlying cellular mechanisms are poorly understood. Using both living fish embryos and mammalian macrophages, we show that processing depends on the shrinkage and packaging of phagosomes into a unique cellular compartment, the gastrosome, with distinct molecular and ultra-structural characteristics.