Widelitz, R. B. | bioRxiv Science

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↗