Biology subjects

Jiang, T.-X.

Publications and source records attributed to Jiang, T.-X..

5 recordsLinked to original sources

bioRxiv2026

A novel reaction-diffusion architecture for engineering self-organized patterns in mammalian cells

Reaction-diffusion circuits generate self-organized spatial patterns through local activation and long-range inhibition, but synthetic implementations in mammalian cells have been limited by the differential-diffusion requirement. Here, we introduce a novel architecture, juxtacrine activation with paracrine inhibition (JAPI), where the activator propagates through cell-cell contacts rather than diffusion. We demonstrate mathematically and numerically that JAPI accesses the same patterning regimes as classical diffusion-based circuits with one fewer free parameter. We then engineer compact synNotch-based JAPI circuits in mammalian fibroblasts and demonstrate their sufficiency for self-organized patterning through tunable, size-limited signal propagation. Functionalized to spatially control morphogen secretion, these circuits perturb feather bud formation on adjacent embryonic chicken epidermis. Finally, we develop a library-based approach to explore coupled, dual-JAPI circuits with tunable cross-inhibition, enabling programmable interactions between patterns and access to a broad morphospace of spatial states. Together, JAPI provides a compact, modular platform for programming self-organized multicellular patterning. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/727552v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@fae8c9org.highwire.dtl.DTLVardef@c8eddborg.highwire.dtl.DTLVardef@177d08corg.highwire.dtl.DTLVardef@11cc952_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2025

Epigenetic Coalitions Couple Tissue Growth to Generate Periodic Colour Patterns in Birds

Periodic patterning is fundamental to biological organization. In birds, colour stripes and spots on growing embryonic surface and elongating feather filaments provide a unique system to study continuous periodic patterning in expanding domains. Agouti-signaling protein (ASIP) directly reports epigenomic activity during colour patterning. Using a neural-network-like architecture, we show that ASIPs cis-regulatory landscape functions as hidden layers, integrating morphogen feedback, chromatin topology, and tissue geometry to generate discrete colour outputs. Single-nucleus multiome and Micro-C uncover stage- and context-specific enhancer-silencer coalitions. Epidermal Wnt ligands activate ASIP while inducing Wnt inhibitors in fibroblasts, forming a negative-feedback loop coupling periodic patterning to domain expansion. Comparative cross-tissue and cross-species analyses define cis-regulatory modules comprising an epigenetic grammar; functional assays highlight retrotransposon co-option expanding ASIPs cis-regulatory repertoire, potentially contributing to colour pattern evolution. Together, these findings motivate a Turing-principle-based communication model: ASIP reflects epigenetic coalitions shifting to drive diverse, environmentally tunable colour motifs for adaptation.

developmental biology↗

bioRxiv2025

Novel Tissue Mechanics-Guided Cellular Flows Enable the Evolution of Feather Follicles

Complex tissue architecture is achieved through multiple rounds of morphological transitions. Here, we analyzed cellular flows and tissue mechanics during avian skin development. We showed how novel cellular flows initiate chemo-mechanical circuits that guide epithelial protrusion, folding, invagination, and spatial cell fate specification. In the initial feather bud formation, stiff dermal condensates protrude vertically out of the locally softened epithelial sheet. As the bud elongates, it stretches the epithelial cells at the base, which mechanically activates YAP and causes the epithelial sheet to fold downward and form a stiff cylindrical wall that invaginates into the skin. This stiff epithelial tongue is essential to the compaction and formation of the tightly packed dermal papillae. These topological transformational events are mechanically interconnected, and the completion of the previous circuit initializes the next one. On the contrary, during scale development, its rigid epithelial sheet restricts dermal cell flows, preventing other further topological transformation. We generated a topological transformation model to show how the process enables the novel evolution of feather follicles.

developmental biology↗

bioRxiv2025

Roles of K-channel activity in feather bud morphogenesis

Bioelectricity plays a key role in shaping tissues during early development. In developing chick skin, we previously demonstrated that a transient standing electrical current loop forms within individual feather buds as they start to elongate. Current flows into the feather bud tip via calcium channels, facilitating collective distal dermal cell movement, thus determining bud orientations. Here, we further evaluate the hypothesis that potassium channels carry the current that flows out of the bud base. We found potassium channel blockers convert periodic feather primordia into horizontal stripes and alter bud aspect ratios by disrupting the bud elongation process. Bioelectric characterization showed the entire current loop is altered, not only the outward current at the base, but also the inward current at the feather bud tip. In situ hybridization shows beta-catenin and Sonic Hedgehog, both feather bud markers, are reduced, resulting in altered periodic patterning and bud shaping. These findings show that a complex multiscale interdependency of ion channel function across a multicellular cell collective is essential for periodic feather patterning and shaping of 3-dimensional feather architecture during skin morphogenesis. Summary StatementCalcium channels at the feather bud tip and potassium channels at the base maintain a standing current loop, creating an essential multicell collective for proper feather bud patterning and morphology.

developmental biology↗

bioRxiv2023

Gap junctions in Turing-type periodic feather pattern formation

Periodic patterning requires coordinated cell-cell interactions at the tissue level. Turing showed, using mathematical modeling, how spatial patterns could arise from the reactions of a diffusive activator-inhibitor pair in an initially homogenous two-dimensional field. Most activators and inhibitors studied in biological systems are proteins, and the roles of cell-cell interaction, ions, bioelectricity, etc. are only now being identified. Gap junctions (GJs) mediate direct exchanges of ions or small molecules between cells, enabling rapid long-distance communications in a cell collective. They are therefore good candidates for propagating non-protein-based patterning signals that may act according to the Turing principles. Here, we explore the possible roles of GJs in Turing-type patterning using feather pattern formation as a model. We found seven of the twelve investigated GJ isoforms are highly dynamically expressed in the developing chicken skin. In ovo functional perturbations of the GJ isoform, connexin 30, by siRNA and the dominant-negative mutant applied before placode development led to disrupted primary feather bud formation, including patches of smooth skin and buds of irregular sizes. Later, after the primary feather arrays were laid out, inhibition of gap junctional intercellular communication in the ex vivo skin explant culture allowed the emergence of new feather buds in temporal waves at specific spatial locations relative to the existing primary buds. The results suggest that gap junctional communication may facilitate the propagation of long-distance inhibitory signals. Thus, the removal of GJ activity would enable the emergence of new feather buds if the local environment is competent and the threshold to form buds is reached. We propose Turing-based computational simulations that can predict the appearance of these ectopic bud waves. Our models demonstrate how a Turing activator-inhibitor system can continue to generate patterns in the competent morphogenetic field when the level of intercellular communication at the tissue scale is modulated.

developmental biology↗