Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.
There are no large datasets associated with this manuscript.
- Terry Lechler
- Terry Lechler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in accordance with recommendation in the Guide for the Care and Use fo Laboratory Animals of the NIH. Animals were handled according to an approved IACUC protocol (A092-18-04) from Duke University.
- Beate Maria Lichtenberger, Medical University of Vienna, Austria
© 2019, Morrow et al.
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