A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo.

During brain development, many newborn neurons undergo apoptosis and are engulfed by microglia, the tissue-resident phagocytes of the brain, in a process known as efferocytosis. A hallmark of microglia is their highly branched morphology characterized by the presence of numerous dynamic extensions that these cells use for scanning the brain parenchyma and engulfing unwanted material. The mechanisms driving branch formation and apoptotic cell engulfment in microglia are unclear.

Conserved exchange of paralog proteins during neuronal differentiation.

Gene duplication enables the emergence of new functions by lowering the evolutionary pressure that is posed on the ancestral genes. Previous studies have highlighted the role of specific paralog genes during cell differentiation, for example, in chromatin remodeling complexes. It remains unexplored whether similar mechanisms extend to other biological functions and whether the regulation of paralog genes is conserved across species.

Going your own way: Self-guidance mechanisms in cell migration.

How cells and tissues migrate from one location to another is a question of significant biological and medical relevance. Migration is generally thought to be controlled by external hardwired guidance cues, which cells follow by polarizing their internal locomotory machinery in the imposed direction. However, a number of recently discovered 'self-guidance' mechanisms have revealed that migrating cells have more control over the path they follow than previously thought.

Smoothelin-like 2 Inhibits Coronin-1B to Stabilize the Apical Actin Cortex during Epithelial Morphogenesis.

The actin cortex is involved in many biological processes and needs to be significantly remodeled during cell differentiation. Developing epithelial cells construct a dense apical actin cortex to carry out their barrier and exchange functions. The apical cortex assembles in response to three-dimensional (3D) extracellular cues, but the regulation of this process during epithelial morphogenesis remains unknown.

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.

Getting back on track: exploiting canalization to uncover the mechanisms of developmental robustness.

Developing embryos can adapt dynamically to noise and variation to generate organs of incredible precision, a process termed 'canalization'; however, the underlying robustness mechanisms are poorly understood. Technological developments, both in quantitative imaging and high precision perturbation, are now enabling targeted investigation into developmental robustness in vivo. Here, we will first distil the common design features of studies that have exploited the canalization behaviour of specific systems to interrogate developmental adaptation, to provide a general experimental framework for future investigations in other contexts.

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.

From morphogen to morphogenesis and back.

A long-term aim of the life sciences is to understand how organismal shape is encoded by the genome. An important challenge is to identify mechanistic links between the genes that control cell-fate decisions and the cellular machines that generate shape, therefore closing the gap between genotype and phenotype. The logic and mechanisms that integrate these different levels of shape control are beginning to be described, and recently discovered mechanisms of cross-talk and feedback are beginning to explain the remarkable robustness of organ assembly.

TimerQuant: a modelling approach to tandem fluorescent timer design and data interpretation for measuring protein turnover in embryos.

Studies on signalling dynamics in living embryos have been limited by a scarcity of in vivo reporters. Tandem fluorescent protein timers provide a generic method for detecting changes in protein population age and thus provide readouts for signalling events that lead to changes in protein stability or location. When imaged with quantitative dual-colour fluorescence microscopy, tandem timers offer detailed 'snapshot' readouts of signalling activity from subcellular to organismal scales, and therefore have the potential to revolutionise studies in developing embryos.

Epithelial Morphogenesis: Stage Diving with Purpose.

In a new paper in the October 8(th) issue of Cell, Kuo and Krasnow (2015) report a previously undescribed mechanism for cell sorting and reveal a dynamic, daredevil behavior of epithelial cells.

Luminal signalling links cell communication to tissue architecture during organogenesis.

Morphogenesis is the process whereby cell collectives are shaped into differentiated tissues and organs. The self-organizing nature of morphogenesis has been recently demonstrated by studies showing that stem cells in three-dimensional culture can generate complex organoids, such as mini-guts, optic-cups and even mini-brains. To achieve this, cell collectives must regulate the activity of secreted signalling molecules that control cell differentiation, presumably through the self-assembly of microenvironments or niches.

Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia.

The removal of dying neurons by microglia has a key role during both development and in several diseases. To date, little is known about the cellular and molecular processes underlying neuronal engulfment in the brain. Here we took a live imaging approach to quantify neuronal cell death progression in embryonic zebrafish brains and studied the response of microglia.

Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.

The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model.

Directional tissue migration through a self-generated chemokine gradient.

The directed migration of cell collectives is a driving force of embryogenesis. The predominant view in the field is that cells in embryos navigate along pre-patterned chemoattractant gradients. One hypothetical way to free migrating collectives from the requirement of long-range gradients would be through the self-generation of local gradients that travel with them, a strategy that potentially allows self-determined directionality.

Collective cell migration in morphogenesis, regeneration and cancer.

The collective migration of cells as a cohesive group is a hallmark of the tissue remodelling events that underlie embryonic morphogenesis, wound repair and cancer invasion. In such migration, cells move as sheets, strands, clusters or ducts rather than individually, and use similar actin- and myosin-mediated protrusions and guidance by extrinsic chemotactic and mechanical cues as used by single migratory cells. However, cadherin-based junctions between cells additionally maintain 'supracellular' properties, such as collective polarization, force generation, decision making and, eventually, complex tissue organization.

EMT 2.0: shaping epithelia through collective migration.

Epithelial-mesenchymal transitions (EMTs) drive epithelial remodelling by converting cohesive, stable epithelial layers into individual, motile mesenchymal cells. It is now becoming clear that, from being an all-or-nothing switch, EMT can be applied in a fine-tuned manner to allow the efficient migration of cohesive epithelia that maintain their internal organisation. Recent work suggests that such collective motility involves a complex balance between epithelial and mesenchyme-like cell states that is driven by internal and external cues.

ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration.

Epimorphic regeneration is a unique and complex instance of postembryonic growth observed in certain metazoans that is usually triggered by severe injury [Akimenko et al., 2003; Alvarado and Tsonis, 2006; Brockes, 1997; Endo et al., 2004].

Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium.

The collective migration of cells in the form of cohesive tissues is a hallmark of both morphogenesis and repair. The extrinsic cues that direct these complex migrations usually act by regulating the dynamics of a specific subset of cells, those at the leading edge. Given that normally the function of tissue migration is to lay down multicellular structures, such as branched epithelial networks or sensory organs, it is surprising how little is known about the mechanisms that organize cells behind the leading edge.

In migrating cells, the Golgi complex and the position of the centrosome depend on geometrical constraints of the substratum.

Although cells migrate in a constrained 3D environment in vivo, in-vitro studies have mainly focused on the analysis of cells moving on 2D substrates. Under such conditions, the Golgi complex is always located towards the leading edge of the cell, suggesting that it is involved in the directional movement. However, several lines of evidence indicate that this location can vary depending on the cell type, the environment or the developmental processes.

The chemokine SDF1a coordinates tissue migration through the spatially restricted activation of Cxcr7 and Cxcr4b.

Tissue migration is a collective behavior that plays a key role in the formation of many organ systems. Although tissue movements are guided by extrinsic cues, in many contexts, their receptors need to be active only at the leading edge to ensure morphogenesis. This has led to the prevalent view that extrinsic signals exert their influence by controlling a small number of leader cells.

Chemokine signaling mediates self-organizing tissue migration in the zebrafish lateral line.

The shape of most complex organ systems arises from the directed migration of cohesive groups of cells. Here, we dissect the role of the chemokine guidance receptor Cxcr4b in regulating the collective migration of one such cohesive tissue, the zebrafish lateral line primordium. Using in vivo imaging, we show that the shape and organization of the primordium is surprisingly labile, and that internal cell movements are uncoordinated in embryos with reduced Cxcr4b signaling.

Organizing moving groups during morphogenesis.

The directed migration of cells drives the formation of many complex organ systems. Although in this morphogenetic context cells display a strong preference for migrating in organized, cohesive groups, little is known about the mechanisms that coordinate their movements. Recent studies on several model systems have begun to dissect the organization of these migrating tissues in vivo and have shown that cell guidance is mediated by a combination of chemical and mechanical cues.

Towing of sensory axons by their migrating target cells in vivo.

Many pathfinding axons must locate target fields that are themselves positioned by active migration. A hypothetical method for ensuring that these migrations are coordinated is towing, whereby the extension of axons is entirely dependent on the migration of their target cells. Here we combine genetics and time-lapse imaging in the zebrafish to show that towing by migrating cells is a bona fide mechanism for guiding pathfinding axons in vivo.