Exocrine gland-resident memory CD8 T cells use mechanosensing for tissue surveillance.

Tissue-resident CD8 T cells (T) continuously scan peptide-MHC (pMHC) complexes in their organ of residence to intercept microbial invaders. Recent data showed that T lodged in exocrine glands scan tissue in the absence of any chemoattractant or adhesion receptor signaling, thus bypassing the requirement for canonical migration-promoting factors. The signals eliciting this noncanonical motility and its relevance for organ surveillance have remained unknown.

Salivary gland macrophages and tissue-resident CD8 T cells cooperate for homeostatic organ surveillance.

It is well established that tissue macrophages and tissue-resident memory CD8 T cells (T) play important roles for pathogen sensing and rapid protection of barrier tissues. In contrast, the mechanisms by which these two cell types cooperate for homeostatic organ surveillance after clearance of infections is poorly understood. Here, we used intravital imaging to show that T dynamically followed tissue macrophage topology in noninflamed murine submandibular salivary glands (SMGs).

ya||a: GPU-Powered Spheroid Models for Mesenchyme and Epithelium.

Simulating morphogenesis of both mesenchyme and epithelium has typically required complex and computationally expensive models. To meet this challenge, we developed ya||a-yet another parallel agent-based model. Our model extends the spheroid model by the addition of spin-like polarities to simulate epithelial sheets and tissue polarity using pairwise interactions only.

The Rho regulator Myosin IXb enables nonlymphoid tissue seeding of protective CD8 T cells.

T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells.

Antigen Availability and DOCK2-Driven Motility Govern CD4 T Cell Interactions with Dendritic Cells In Vivo.

Parenchymal migration of naive CD4 T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3Kγ and is widely assumed to facilitate efficient screening of dendritic cells (DCs) presenting peptide-MHCs (pMHCs). Yet how CD4 T cell motility, DC density, and pMHC levels interdependently regulate such interactions has not been comprehensively examined. Using intravital imaging of reactive LNs in DC-immunized mice, we show that pMHC levels determined the occurrence and timing of stable CD4 T cell-DC interactions.

Distribution of neurosensory progenitor pools during inner ear morphogenesis unveiled by cell lineage reconstruction.

Reconstructing the lineage of cells is central to understanding how the wide diversity of cell types develops. Here, we provide the neurosensory lineage reconstruction of a complex sensory organ, the inner ear, by imaging zebrafish embryos in vivo over an extended timespan, combining cell tracing and cell fate marker expression over time. We deliver the first dynamic map of early neuronal and sensory progenitor pools in the whole otic vesicle.

Simulating tissue morphogenesis and signaling.

During embryonic development tissue morphogenesis and signaling are tightly coupled. It is therefore important to simulate both tissue morphogenesis and signaling simultaneously in in silico models of developmental processes. The resolution of the processes depends on the questions of interest.

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.

The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse.

How do digits emerge? - mathematical models of limb development.

The mechanism that controls digit formation has long intrigued developmental and theoretical biologists, and many different models and mechanisms have been proposed. Here we review models of limb development with a specific focus on digit and long bone formation. Decades of experiments have revealed the basic signaling circuits that control limb development, and recent advances in imaging and molecular technologies provide us with unprecedented spatial detail and a broader view of the regulatory networks.

Digit patterning during limb development as a result of the BMP-receptor interaction.

Turing models have been proposed to explain the emergence of digits during limb development. However, so far the molecular components that would give rise to Turing patterns are elusive. We have recently shown that a particular type of receptor-ligand interaction can give rise to Schnakenberg-type Turing patterns, which reproduce patterning during lung and kidney branching morphogenesis.