title: Egf Signaling Directs Neoblast Repopulation by Regulating Asymmetric Cell Division in Planarians.
abstract: A large population of proliferative stem cells (neoblasts) is required for physiological tissue homeostasis and post-injury regeneration in planarians. Recent studies indicate that survival of a few neoblasts after sublethal irradiation results in the clonal expansion of the surviving stem cells and the eventual restoration of tissue homeostasis and regenerative capacity. However, the precise mechanisms regulating the population dynamics of neoblasts remain largely unknown. Here, we uncovered a central role for epidermal growth factor (EGF) signaling during in vivo neoblast expansion mediated by Smed-egfr-3 (egfr-3) and its putative ligand Smed-neuregulin-7 (nrg-7). Furthermore, the EGF receptor-3 protein localizes asymmetrically on the cytoplasmic membrane of neoblasts, and the ratio of asymmetric to symmetric cell divisions decreases significantly in egfr-3(RNAi) worms. Our results not only provide the first molecular evidence of asymmetric stem cell divisions in planarians, but also demonstrate that EGF signaling likely functions as an essential regulator of neoblast clonal expansion.
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA. Electronic address: kle@stowers.org.
authors: Kai
authors: K
authors: Lei
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Hanh
authors: H
authors: Thi-Kim Vu
authors: Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
authors: Ryan D
authors: RD
authors: Mohan
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Sean A
authors: SA
authors: McKinney
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Chris W
authors: CW
authors: Seidel
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Richard
authors: R
authors: Alexander
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Kirsten
authors: K
authors: Gotting
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors: Jerry L
authors: JL
authors: Workman
authors: Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Howard Hughes Medical Institute, Stowers Institute for Medical Research, Kansas City, MO 64110, USA. Electronic address: asa@stowers.org.
authors: Alejandro
authors: A
authors: Sánchez Alvarado
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D060049:Asymmetric Cell Division / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004265:DNA Helicases / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D042822:Genomic Instability / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism; D010932:Planarians / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000528:radiation effects
chemical_list: D015801:Helminth Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D004265:DNA Helicases
keywords: epidermal growth factor; extracellular signaling; neoblast regeneration; regeneration; stem cell repopulation; sublethal irradiation