Global cell sorting is mediated by local cell–cell interactions in the C. elegans embryo

AbstractThe Caenorhabditis elegans embryo achieves pattern formation by sorting cells into coherent regions before morphogenesis is initiated. The sorting of cells is coupled to their fate. Cells move extensively relative to each other to reach their correct position in the body plan. Analyzing the mechanism of cell sorting in in vitro culture experiments using 4D microscopy, we show that all AB-derived cells sort only according to their local neighbors, and that all cells are able to communicate with each other. The directions of cell movement do not depend on a cellular polarity but only on local cell–cell interactions; in experimental situations, this allows even the reversal of the polarity of whole regions of the embryo. The work defines a new mechanism of pattern formation we call “cell focusing”

Expression of different L1 isoforms of Mastomys natalensis papillomavirus as mechanism to circumvent adaptive immunity

Although many high-risk mucosal and cutaneous human papillomaviruses (HPVs) theoretically have the potential to synthesize L1 isoforms differing in length, previous seroepidemiological studies only focused on the short L1 variants, co-assembling with L2 to infectious virions. Using the multimammate mouse Mastomys coucha as preclinical model, this is the first study demonstrating seroconversion against different L1 isoforms during the natural course of papillomavirus infection. Intriguingly, positivity with the cutaneous MnPV was accompanied by a strong seroresponse against a longer L1 isoform, but to our surprise, the raised antibodies were non-neutralizing. Only after a delay of around 4 months, protecting antibodies against the short L1 appeared, enabling the virus to successfully establish an infection. This argues for a novel humoral immune escape mechanism that may also have important implications on the interpretation of epidemiological data in terms of seropositivity and protection of PV infections in general.Fil: Fu, Yingying. German Cancer Research Center; AlemaniaFil: Cao, Rui. German Cancer Research Center; AlemaniaFil: Schäfer, Miriam. German Cancer Research Center; AlemaniaFil: Stephan, Sonja. German Cancer Research Center; AlemaniaFil: Braspenning Wesch, Ilona. German Cancer Research Center; AlemaniaFil: Schmitt, Laura. German Cancer Research Center; AlemaniaFil: Bischoff, Ralf. German Cancer Research Center; AlemaniaFil: Müller, Martin. German Cancer Research Center; AlemaniaFil: Schäfer, Kai. German Cancer Research Center; AlemaniaFil: Vinzon, Sabrina Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rösl, Frank. German Cancer Research Center; AlemaniaFil: Hasche, Daniel. German Cancer Research Center ; Alemani

A Posterior Centre Establishes and Maintains Polarity of the Caenorhabditis elegans Embryo by a Wnt-Dependent Relay Mechanism

Cellular polarity is a general feature of animal development. However, the mechanisms that establish and maintain polarity in a field of cells or even in the whole embryo remain elusive. Here we provide evidence that in the Caenorhabditis elegans embryo, the descendants of P(1), the posterior blastomere of the 2-cell stage, constitute a polarising centre that orients the cell divisions of most of the embryo. This polarisation depends on a MOM-2/Wnt signal originating from the P(1) descendants. Furthermore, we show that the MOM-2/Wnt signal is transduced from cell to cell by a relay mechanism. Our findings suggest how polarity is first established and then maintained in a field of cells. According to this model, the relay mechanism constantly orients the polarity of all cells towards the polarising centre, thus organising the whole embryo. This model may also apply to other systems such as Drosophila and vertebrates

Automated Laser‐Transfer Synthesis of High‐Density Microarrays for Infectious Disease Screening

Laser-induced forward transfer (LIFT) is a rapid laser-patterning technique for high-throughput combinatorial synthesis directly on glass slides. A lack of automation and precision limits LIFT applications to simple proof-of-concept syntheses of fewer than 100 compounds. Here, an automated synthesis instrument is reported that combines laser transfer and robotics for parallel synthesis in a microarray format with up to 10 000 individual reactions cm−2. An optimized pipeline for amide bond formation is the basis for preparing complex peptide microarrays with thousands of different sequences in high yield with high reproducibility. The resulting peptide arrays are of higher quality than commercial peptide arrays. More than 4800 15-residue peptides resembling the entire Ebola virus proteome on a microarray are synthesized to study the antibody response of an Ebola virus infection survivor. Known and unknown epitopes that serve now as a basis for Ebola diagnostic development are identified. The versatility and precision of the synthesizer is demonstrated by in situ synthesis of fluorescent molecules via Schiff base reaction and multi-step patterning of precisely definable amounts of fluorophores. This automated laser transfer synthesis approach opens new avenues for high-throughput chemical synthesis and biological screening