Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length

Animal cells within a tissue typically display a striking regularity in their size. To date, the molecular mechanisms that control this uniformity are still unknown. We have previously shown that size uniformity in animal cells is promoted, in part, by size-dependent regulation of G1 length. To identify the molecular mechanisms underlying this process, we performed a large-scale small molecule screen and found that the p38 MAPK pathway is involved in coordinating cell size and cell cycle progression. Small cells display higher p38 activity and spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of the compensatory G1 length extension in small cells, resulting in faster proliferation, smaller cell size and increased size heterogeneity. We propose a model wherein the p38 pathway responds to changes in cell size and regulates G1 exit accordingly, to increase cell size uniformity

Characterizing Murine Compensatory Renal Growth following Unilateral Nephrectomy

Following the surgical removal of a single kidney, the remaining kidney shows a striking ability to compensate for this loss by rapidly initiating an acute growth program, coupled with increased function. The organ size change halts once normal function is restored, but the signals regulating this change in kidney size remain unknown. This work describes murine compensatory renal growth on the level of organ size, function, and cellular changes up to 28 days post-surgery. The data suggests that the extent of remnant kidney growth may be related to the ratio of kidney weight-to-body weight prior to surgery, potentially hinting at a predictive factor of postoperative renal mass recovery and implicating a size sensing mechanism in this process. We also developed an image processing pipeline to analyze kidney cross-sections, and identified trends in nuclear size and density changes, suggesting the contribution of both hypertrophy and hyperplasia to compensatory renal growth.M.Sc