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Biology subjects

Skokan, T. D.

Publications and source records attributed to Skokan, T. D..

3 recordsLinked to original sources

Luminal epithelium remodeling underlies endometrial regeneration during menstruation and pregnancy

Menstruation and pregnancy impose an immense regenerative burden on the endometrium. These events breach the luminal epithelium lining the uterine cavity, which is proposed to be replenished by cells in adjoining epithelial glands. In contrast to this gland-centric model, we find that luminal and glandular epithelia are maintained by separate progenitor populations during homeostasis, induced menstruation, pregnancy, and postpartum repair in mice. Although our data indicate that gland cells do not contribute substantially to luminal epithelium regeneration under physiological conditions, we find that they can serve as facultative progenitors that resurface the tissue after chemical ablation. During menstruation, the luminal epithelium bypasses the need for gland contributions by undergoing extensive expansion and morphogenesis to re-epithelialize stromal surfaces concurrently with tissue breakdown. Analogous morphogenesis occurs during gestation, revealing luminal epithelial expansion as a unifying mechanism enabling simultaneous stromal disruption and re-epithelialization, which may underlie the endometrium's remarkable regenerative capacity.

developmental biology↗

Mechanical stretch regulates macropinocytosis in Hydra vulgaris

Cells rely on a diverse array of engulfment processes to sense, exploit, and adapt to their environments. Macropinocytosis is a versatile example of such a process, allowing for the indiscriminate and rapid uptake of large volumes of fluid and membrane. Much of the molecular machinery essential for macropinocytosis has been well established. However, most of these studies relied on tissue culture models, leaving the regulation of this process within the context of organs and organisms unresolved. Here, we report that large-scale macropinocytosis occurs in the outer epithelial layer of the cnidarian Hydra vulgaris. Exploiting Hydras relatively simple body plan, we developed approaches to visualize macropinocytosis over extended periods of time in living tissue, revealing constitutive engulfment across the entire body axis. Using pharmacological perturbations, we establish a role for stretch-activated channels, including Piezo, and downstream calcium influx in inhibiting this process. Finally, we show that the direct application of planar stretch leads to calcium influx and a corresponding inhibition of macropinocytosis. Together, our approaches provide a platform for the mechanistic dissection of constitutive macropinocytosis in physiological contexts and reveal a role for macropinocytosis in responding to membrane tension.

cell biology↗

Tissue-specific degradation of essential centrosome components reveals distinct microtubule populations at microtubule organizing centers

Non-centrosomal microtubule organizing centers (ncMTOCs) are found in most differentiated cells, but how these structures regulate microtubule organization and dynamics is largely unknown. We optimized a tissue-specific degradation system to test the role of the essential centrosomal microtubule nucleators {gamma}-tubulin ring complex ({gamma}-TURC) and AIR-1/Aurora A at the apical ncMTOC, where they both localize in C. elegans embryonic intestinal epithelial cells. As at the centrosome, the core {gamma}-TURC component GIP-1/GCP3 is required to recruit other {gamma}-TuRC components to the apical ncMTOC including MZT-1/MZT1, characterized here for the first time in animal development. In contrast, AIR-1 and MZT-1 were specifically required to recruit {gamma}-TuRC to the centrosome, but not to centrioles or to the apical ncMTOC. Surprisingly, microtubules remain robustly organized at the apical ncMTOC upon {gamma}-TuRC and AIR-1 co-depletion, and upon depletion of other known microtubule regulators including TPXL-1/TPX2, ZYG-9/chTOG, PTRN-1/CAMSAP, and NOCA-1/Ninein. However, loss of GIP-1 removed a subset of dynamic EBP-2/EB1-marked microtubules, and the remaining dynamic microtubules grew faster. Together, these results suggest that different MTOCs use discrete proteins for their function, and that the apical ncMTOC is composed of distinct populations of {gamma}-TuRC-dependent and independent microtubules that compete for a limited pool of resources.

cell biology↗