jonmoulton @jonmoulton@qoto.org

A monthly journal publishing high-quality, peer-reviewed research on all topics related to RNA and its metabolism in all organisms

Abstract. The field of synthetic nucleic acids with novel backbone structures [xenobiotic nucleic acids (XNAs)] has flourished due to the increased importance o

Biological processes are regulated by chemical signals (e.g., morphogens, growth factors, and guidance cues) and mechanical signals (e.g., tissue stiffness and cellular forces). Yet, the interaction between these two signals in vivo remains poorly understood. Using the developing Xenopus laevis brain as a model system, where growing retinal ganglion cell (RGC) axons are guided by both chemical and mechanical cues, we demonstrate that knockdown of the mechanosensitive ion channel, Piezo1, exerts cell-intrinsic and cell-extrinsic effects on axon pathfinding. Targeted Piezo1 knockdown in RGCs led to pathfinding errors in vivo. However, pathfinding errors were also observed in RGCs expressing Piezo1, when Piezo1 was downregulated in the surrounding brain tissue. Depleting Piezo1 levels led to both a decrease in the expression of the long-range chemical guidance cues, Semaphorin3A (Sema3A) and Slit1, and a decrease in tissue stiffness. While tissue softening was independent of Sema3A depletion, Slit1 and Sema3A expression increased significantly in stiffer environments in vitro. Moreover, stiffening soft brain regions in vivo induced ectopic production of Sema3A, via a Piezo1-dependent mechanism. Our results show that brain tissue mechanics modulates the expression of key chemical cues. This dynamic interplay between tissue mechanics and long-range chemical signalling likely extends across diverse biological systems throughout development, homeostasis, and disease. ### Competing Interest Statement The authors have declared no competing interest.

Vertebrate motile cilia are broadly classified as (9+2) or (9+0), based on the presence or absence of the central pair apparatus, respectively. Cryogenic electron microscopy (cryo-EM) analyses of (9+2) cilia have uncovered an elaborate axonemal protein composition; whether these features are relevant to (9+0) cilia remain unclear. We previously demonstrated that Cfap53, a key microtubule inner protein (MIP) as well as centriolar-satellites component, is essential for motility of (9+0), but not (9+2) cilia. Here, we show that in (9+2) cilia, Cfap53 functions redundantly with a paralogous MIP, Mns1. Mns1 localizes to ciliary axonemes, and combined loss of both proteins in zebrafish and mice, caused severe loss of outer dynein arms (ODAs) of (9+2) cilia, significantly affecting their motility. Moreover, using immunoprecipitation, we demonstrate that while Mns1 can self-associate and interact with Cfap53, Cfap53 is unable to self-associate. Finally, we show that multiple additional dynein interacting proteins, such as the ODA docking complex (ODA-DC) members, show strikingly distinct localization patterns between various motile cilia-types. Our findings clarify how paralogous MIPs, Cfap53 and Mns1, function in regulating motility of (9+2) versus (9+0) cilia, and establish that localization pattern of other key motility proteins also differ between these cilia-types, further emphasizing extensive structural variations among these organelles. ### Competing Interest Statement The authors have declared no competing interest.

Abstract. Complex biological processes are regulated by both genetic and epigenetic programs. One class of epigenetic modifications is methylation. Evolutionari

The Momentum trial from Sarepta Therapeutics is investigating SRP-5051 (vesleteplirsen) for use among male patients aged 8 to 21 years who have Duchenne muscular dystrophy amenable to exon 51 skipping.

Convergent extension of the chordamesoderm is the best-examined gastrulation movement in Xenopus. Here we study general features of cell-cell contacts in this tissue by combining depletion of adhesion factors C-cadherin, Syndecan-4, fibronectin, and hyaluronic acid, the analysis of respective contact width spectra and contact angles, and La3+ staining of the pericellular matrix. We provide evidence that like in other gastrula tissues, cell-cell adhesion in the chordamesoderm is largely mediated by different types of pericellular matrix. Specific glycocalyx structures previously identified in Xenopus gastrula tissues are absent in chordamesoderm but other contact types like 10–20 nm wide La3+ stained structures are present instead. Knockdown of any of the adhesion factors reduces the abundance of cell contacts but not the average relative adhesiveness of the remaining ones: a decrease of adhesiveness at low contact widths is compensated by an increase of contact widths and an increase of adhesiveness proportional to width. From the adhesiveness-width relationship, we derive a model of chordamesoderm cell adhesion that involves the interdigitation of distinct pericellular matrix units. Quantitative description of pericellular matrix deployment suggests that reduced contact abundance upon adhesion factor depletion is correlated with excessive accumulation of matrix material in non-adhesive gaps and the loss of some contact types.