Despite many advances in understanding stem cell regulation and growth signalling, the developmental mechanisms controlling organ size attainment remain elusive. How does an organism know when the appropriate number of cells in an organ has been reached, either during development or regeneration? In this issue (p. ), Christian Petersen and Eric Hill describe a novel system to investigate whole cell number control during organ regeneration in the planarian. In their study, the authors report how a specific ratio of brain neurons to body size is maintained during periods of organismal growth, shrinking and regeneration. Using this foundation, the authors demonstrate how wnt11-6 (expressed at the posterior of the brain) and the Wnt inhibitor notum (expressed at the anterior of the brain) co-regulate each other and ultimately determine brain size. Further, the authors show this is not through cell proliferation or death, but through a pathway involving canonical and non-canonical Wnt signalling that influences neural progenitor numbers. Taken together, these results illustrate a genetic mechanism for the loss of cell number during regeneration and show how stem cell regulation can be responsible for organ size reduction.
