An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians

Dev Cell. 2012 Oct 16;23(4):691-704. doi: 10.1016/j.devcel.2012.09.008.

Abstract

Planarians grow and regenerate organs by coordinating proliferation and differentiation of pluripotent stem cells with remodeling of postmitotic tissues. Understanding how these processes are orchestrated requires characterizing cell-type-specific gene expression programs and their regulation during regeneration and homeostasis. To this end, we analyzed the expression profile of planarian intestinal phagocytes, cells responsible for digestion and nutrient storage/distribution. Utilizing RNA interference, we identified cytoskeletal regulators required for intestinal branching morphogenesis and a modulator of bioactive sphingolipid metabolism, ceramide synthase, required for the production of functional phagocytes. Additionally, we found that a gut-enriched homeobox transcription factor, nkx-2.2, is required for somatic stem cell proliferation, suggesting a niche-like role for phagocytes. Identification of evolutionarily conserved regulators of intestinal branching, differentiation, and stem cell dynamics demonstrates the utility of the planarian digestive system as a model for elucidating the mechanisms controlling postembryonic organogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation*
  • Cytoskeletal Proteins / metabolism*
  • Gene Expression Profiling
  • Homeodomain Proteins / metabolism
  • Intestine, Small / cytology*
  • Intestine, Small / growth & development*
  • Intestine, Small / metabolism
  • Morphogenesis
  • Oxidoreductases / metabolism
  • Planarians / cytology*
  • Planarians / metabolism
  • RNA Interference*
  • Sphingolipids / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription Factors / metabolism
  • Zebrafish Proteins

Substances

  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • Nkx2.2 protein
  • Sphingolipids
  • Transcription Factors
  • Zebrafish Proteins
  • Oxidoreductases
  • dihydroceramide desaturase

Associated data

  • GEO/GSE35565