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Publication : Regulated spindle orientation buffers tissue growth in the epidermis.

First Author  Morrow A Year  2019
Journal  Elife Volume  8
PubMed ID  31577227 Mgi Jnum  J:290859
Mgi Id  MGI:6435584 Doi  10.7554/eLife.48482
Citation  Morrow A, et al. (2019) Regulated spindle orientation buffers tissue growth in the epidermis. Elife 8:e48482
abstractText  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.
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