Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation

Curr Biol. 2010 Sep 14;20(17):1580-7. doi: 10.1016/j.cub.2010.07.041. Epub 2010 Aug 19.

Abstract

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 [3-5]. If the midgut epithelium is damaged, then ISC proliferation increases [6-12]. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / physiology*
  • Drosophila Proteins / physiology*
  • Intestines / physiology*
  • Nuclear Proteins / physiology*
  • Protein Kinases / physiology*
  • Regeneration*
  • Stem Cells / cytology*
  • Trans-Activators / physiology*

Substances

  • Drosophila Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Yki protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila