Hedgehog signaling regulates imaginal cell differentiation in a basally branching holometabolous insect

Dev Biol. 2015 Aug 15;404(2):125-35. doi: 10.1016/j.ydbio.2015.05.020. Epub 2015 May 27.


The evolution of imaginal cells, or stem cell-like cells, contributed to the spectacular diversification of holometabolous insects, which undergo complete metamorphosis. The proliferation and differentiation of these imaginal cells is under the control of juvenile hormone (JH), but which patterning genes respond to JH is currently unknown. Here, the role of Hedgehog (Hh) signaling in the development of imaginal cells was investigated. RNA interference-mediated knockdown of the components of the Hh signaling pathway showed that Hh is required for the proliferation of polymorphic and imaginal cells in Tribolium castaneum. Hh was also necessary for the regeneration of larval appendages. In contrast, knockdown of Hh signaling antagonists, patched and costal 2 led to the overgrowth and precocious maturation of structures derived from imaginal cells and the occasional appearance of ectopic appendages from the head epidermis. In addition, JH suppressed the expression of hh both in vivo and in vitro. Our findings suggest that imaginal cells are created and maintained by modulating Hh signaling. Thus, Hh signaling may have played a critical role during the evolution of complete metamorphosis.

Keywords: Hedgehog (Hh) signaling; Imaginal cells; Juvenile hormone (JH); Metamorphosis; Tribolium castaneum.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Imaginal Discs / cytology*
  • Insect Proteins / genetics
  • Juvenile Hormones / genetics*
  • Kinesins / genetics
  • Larva / growth & development
  • Metamorphosis, Biological / genetics*
  • Metamorphosis, Biological / physiology
  • Patched Receptors
  • Pupa / growth & development
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Cell Surface / genetics
  • Regeneration / genetics
  • Signal Transduction
  • Tribolium / embryology*


  • Hedgehog Proteins
  • Insect Proteins
  • Juvenile Hormones
  • Patched Receptors
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Kinesins