What are you synching about? Emerging complexity of Notch signaling in the segmentation clock.

The Segmentation clock is a population of cellular genetic oscillators, located in the posterior of the elongating vertebrate embryo, that governs the rhythmic and sequential segmentation of the body axis into somites. Somites are blocks of cells that give rise to the segmented anatomy of the adult, including the backbone, muscles and skin. Malfunction of the segmentation clock results in malformations of these structures, a condition termed congenital scoliosis in the clinic. In all vertebrates, the oscillating cells of the segmentation clock are coordinated in a wave pattern, such that each new wave corresponds to a new segment. Maintenance of this wave pattern is important for precise segmentation and requires the local synchronization of the cellular oscillators. Existing models of the segmentation clock have explored the role of the Delta-Notch intercellular signaling pathway primarily as a coupling mechanism between neighboring autonomous oscillators. Recent work challenges several aspects of this simplification, suggesting that the mechanism of synchronization is more complex and may differ between species, and that Notch signaling may do more than synchronize cells. Here, we first examine evidence and models concerning the role of Notch signaling in driving, maintaining and synchronizing the mouse clock, highlighting results emerging from ex vivo culture systems of mouse segmentation clock cells. We then compare this to synchronization in the zebrafish, where accumulating evidence suggests that Notch signaling impacts the amplitude of the oscillating signal, and discuss whether the amplitude itself is meaningful for segmentation. Finally, we review work showing that multiple Delta ligands are active in segmentation, and consider how an interplay between these ligands could confer effective Notch functions in the segmentation clock. These lines of enquiry suggest that synchronization and Notch signaling are more complex than previously described, and reveal exciting new avenues for investigation into the coordination and precision of patterning the early embryo.

Generation of patterns in the paraxial mesoderm.

The Segmentation Clock is a tissue-level patterning system that enables the segmentation of the vertebral column precursors into transient multicellular blocks called somites. This patterning system comprises a set of elements that are essential for correct segmentation. Under the so-called "Clock and Wavefront" model, the system consists of two elements, a genetic oscillator that manifests itself as traveling waves of gene expression, and a regressing wavefront that transforms the temporally periodic signal encoded in the oscillations into a permanent spatially periodic pattern of somite boundaries. Over the last twenty years, every new discovery about the Segmentation Clock has been tightly linked to the nomenclature of the "Clock and Wavefront" model. This constrained allocation of discoveries into these two elements has generated long-standing debates in the field as what defines molecularly the wavefront and how and where the interaction between the two elements establishes the future somite boundaries. In this review, we propose an expansion of the "Clock and Wavefront" model into three elements, "Clock", "Wavefront" and signaling gradients. We first provide a detailed description of the components and regulatory mechanisms of each element, and we then examine how the spatiotemporal integration of the three elements leads to the establishment of the presumptive somite boundaries. To be as exhaustive as possible, we focus on the Segmentation Clock in zebrafish. Furthermore, we show how this three-element expansion of the model provides a better understanding of the somite formation process and we emphasize where our current understanding of this patterning system remains obscure.

Open-source microscope add-on for structured illumination microscopy.

Super-resolution techniques expand the abilities of researchers who have the knowledge and resources to either build or purchase a system. This excludes the part of the research community without these capabilities. Here we introduce the openSIM add-on to upgrade existing optical microscopes to Structured Illumination super-resolution Microscopes (SIM). The openSIM is an open-hardware system, designed and documented to be easily duplicated by other laboratories, making super-resolution modality accessible to facilitate innovative research. The add-on approach gives a performance improvement for pre-existing lab equipment without the need to build a completely new system.