Tissue mechanics drive morphogenesis, but how forces are sensed and transmitted to control stem cell fate and self-organization remains unclear. We show that a mechanosensory complex of emerin (Emd), non-muscle myosin IIA (NMIIA) and actin controls gene silencing and chromatin compaction, thereby regulating lineage commitment. Force-driven enrichment of Emd at the outer nuclear membrane of epidermal stem cells leads to defective heterochromatin anchoring to the nuclear lamina and a switch from H3K9me2,3 to H3K27me3 occupancy at constitutive heterochromatin. Emd enrichment is accompanied by the recruitment of NMIIA to promote local actin polymerization that reduces nuclear actin levels, resulting in attenuation of transcription and subsequent accumulation of H3K27me3 at facultative heterochromatin. Perturbing this mechanosensory pathway by deleting NMIIA in mouse epidermis leads to attenuated H3K27me3-mediated silencing and precocious lineage commitment, abrogating morphogenesis. Our results reveal how mechanics integrate nuclear architecture and chromatin organization to control lineage commitment and tissue morphogenesis.

The development of modern high-throughput instrumentation and improved core facility infrastructures leads to an accumulation of large amounts of scientific data. However, for a majority of scientists the comprehensive analysis and visualization of their data goes beyond their expertise. To reduce this hurdle, we developed a software suite called Instant Clue that helps scientists to visually analyze data and to gain insights into biological processes from their high-dimensional dataset. Instant Clue combines the power of visual and statistical analytics using a straight forward drag & drop approach making the software highly intuitive. Additionally, it offers a comprehensive portfolio of statistical tools for systematic analysis such as dimensional reduction, (un)-supervised learning, clustering, multi-block (omics) integration and curve fitting. Charts can be combined with high flexibility into a main figure template for direct usage in scientific publications. Even though Instant Clue was developed with the omics-sciences in mind, users can analyze any kind of data from low to high dimensional data sets. The open-source software is available for Windows and Mac OS (http://www.instantclue.uni-koeln.de) and is accompanied by a detailed video tutorial series.

Communication between individuals via molecules, termed chemosignaling, is widespread among animal and plant species. However, we lack knowledge on the specific functions of the substances involved for most systems. The femoral gland is an organ that secretes a waxy substance involved in chemical communication in lizards. While the lipids and volatile substances secreted by the femoral glands have been investigated in several biochemical studies, the protein composition and functions of secretions remain completely unknown. Applying a proteomic approach, we provide the first attempt to comprehensively characterize the protein composition of femoral gland secretions from the Galápagos marine iguana. Using samples from several organs, the marine iguana proteome was assembled by next-generation sequencing and mass spectrometry, resulting in 7,513 proteins. Of these, 4,305 proteins were present in the femoral gland, including keratins, small serum proteins, and fatty acid-binding proteins. Surprisingly, no proteins with discernible roles in partner recognition or inter-species communication could be identified. However, we did find several proteins with direct associations to the innate immune system, including lysozyme C, antileukoproteinase (ALP), pulmonary surfactant protein (SFTPD), and galectin (LGALS1) suggesting that the femoral glands function as an important barrier to infection. Furthermore, we report several novel anti-microbial peptides from the femoral glands that show similar action against Escherichia coli and Bacillus subtilis such as oncocin, a peptide known for its effectiveness against Gram-negative pathogens. This proteomics dataset is a valuable resource for future functional protein analysis and demonstrates that femoral gland secretions also perform functions of the innate immune system.