EGFR signaling regulates cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis

Dev Biol. 2011 Jun 1;354(1):87-101. doi: 10.1016/j.ydbio.2011.03.023. Epub 2011 Mar 31.


Similarly to development, the process of regeneration requires that cells accurately sense and respond to their external environment. Thus, intrinsic cues must be integrated with signals from the surrounding environment to ensure appropriate temporal and spatial regulation of tissue regeneration. Identifying the signaling pathways that control these events will not only provide insights into a fascinating biological phenomenon but may also yield new molecular targets for use in regenerative medicine. Among classical models to study regeneration, freshwater planarians represent an attractive system in which to investigate the signals that regulate cell proliferation and differentiation, as well as the proper patterning of the structures being regenerated. Recent studies in planarians have begun to define the role of conserved signaling pathways during regeneration. Here, we extend these analyses to the epidermal growth factor (EGF) receptor pathway. We report the characterization of three epidermal growth factor (EGF) receptors in the planarian Schmidtea mediterranea. Silencing of these genes by RNA interference (RNAi) yielded multiple defects in intact and regenerating planarians. Smed-egfr-1(RNAi) resulted in decreased differentiation of eye pigment cells, abnormal pharynx regeneration and maintenance, and the development of dorsal outgrowths. In contrast, Smed-egfr-3(RNAi) animals produced smaller blastemas associated with abnormal differentiation of certain cell types. Our results suggest important roles for the EGFR signaling in controlling cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation*
  • Cell Proliferation*
  • ErbB Receptors / classification
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Homeostasis
  • In Situ Hybridization
  • Molecular Sequence Data
  • Morphogenesis
  • Phylogeny
  • Planarians / embryology
  • Planarians / growth & development
  • Planarians / physiology*
  • Protein Isoforms / classification
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • RNA Interference
  • Regeneration*
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • Helminth Proteins
  • Protein Isoforms
  • ErbB Receptors

Associated data

  • GENBANK/HM777016
  • GENBANK/HM777017
  • GENBANK/HM777018