Current Biology
Volume 20, Issue 17, 14 September 2010, Pages 1580-1587
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Warts and Yorkie Mediate Intestinal Regeneration by Influencing Stem Cell Proliferation

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Summary

Homeostasis in the Drosophila midgut is maintained by stem cells [1, 2]. The intestinal epithelium contains two types of differentiated cells that are lost and replenished: enteroendocrine (EE) cells and enterocytes (ECs). Intestinal stem cells (ISCs) are the only cells in the adult midgut that proliferate [3, 4], and ISC divisions give rise to an ISC and an enteroblast (EB), which differentiates into an EC or an EE cell [3, 4, 5]. If the midgut epithelium is damaged, then ISC proliferation increases [6, 7, 8, 9, 10, 11, 12]. Damaged ECs express secreted ligands (Unpaired proteins) that activate Jak-Stat signaling in ISCs and EBs to promote their proliferation and differentiation [7, 9, 13, 14]. We show that the Hippo pathway components Warts and Yorkie mediate a transition from low- to high-level ISC proliferation to facilitate regeneration. The Hippo pathway regulates growth in diverse organisms and has been linked to cancer [15, 16]. Yorkie is activated in ECs in response to tissue damage or activation of the damage-sensing Jnk pathway. Activation of Yorkie promotes expression of unpaired genes and triggers a nonautonomous increase in ISC proliferation. Our observations uncover a role for Hippo pathway components in regulating stem cell proliferation and intestinal regeneration.

Highlights

► Warts and Yorkie influence stem cell proliferation in the Drosophila intestine ► Warts and Yorkie control the expression of cytokines for the Jak-Stat pathway ► Yorkie is activated by tissue damage and the damage-sensing Jnk pathway ► Warts and Yorkie link a stem cell-mediated regenerative response to tissue damage

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