Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain

Elife. 2016 Nov 19;5:e19735. doi: 10.7554/eLife.19735.


The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, Smed-nkx2.1 and Smed-arx, which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian hedgehog ligand (Smed-hh), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core hh signal transduction genes, and consistent hh signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian hh signaling molecule in the adult CNS.

Keywords: developmental biology; flatworms; planarians; schmidtea mediterranea; stem cells; triclads.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiology*
  • Hedgehog Proteins / metabolism*
  • Homeodomain Proteins / metabolism
  • Neurogenesis*
  • Neurons / physiology*
  • Platyhelminths / physiology*
  • Transcription Factors / metabolism


  • Hedgehog Proteins
  • Homeodomain Proteins
  • Transcription Factors

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.