title: Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation.
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.
authors: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Binnaz Kucuk
authors: BK
authors: Staley
authors: Kenneth D
authors: KD
authors: Irvine
mesh_terms: D000818:Animals; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D007422:Intestines / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D015534:Trans-Activators / Q000502:physiology*; D000091102:YAP-Signaling Proteins
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; D011494:Protein Kinases; C093503:wts protein, Drosophila