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Biology subjects

Zitting, M.

Publications and source records attributed to Zitting, M..

2 recordsLinked to original sources

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↗

Balancing dynamic tradeoffs to drive cellular reprogramming

Although cellular reprogramming continues to generate new cell types, reprogramming remains a rare cellular event. The molecular mechanisms that limit reprogramming, particularly to somatic lineages, remain unclear. By examining fibroblast-to-motor neuron conversion, we identify a previously unappreciated dynamic between transcription and replication that determines reprogramming competency. Transcription factor overexpression forces most cells into states that are refractory to reprogramming and are characterized by either hypertranscription with little cell division, or hyperproliferation with low transcription. We identify genetic and chemical factors that dramatically increase the number of cells capable of both hypertranscription and hyperproliferation. Hypertranscribing, hyperproliferating cells reprogram at 100-fold higher, near-deterministic rates. We demonstrate that elevated topoisomerase expression endows cells with privileged reprogramming capacity, suggesting that biophysical constraints limit cellular reprogramming to rare events.

cell biology↗