An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians.
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.
Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
David J
DJ
Forsthoefel
Noëlle P
NP
James
David J
DJ
Escobar
Joel M
JM
Stary
Ana P
AP
Vieira
Forrest A
FA
Waters
Phillip A
PA
Newmark
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D009024:Morphogenesis; D010088:Oxidoreductases / Q000378:metabolism; D010932:Planarians / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D013107:Sphingolipids / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D029961:Zebrafish Proteins
D003598:Cytoskeletal Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D013107:Sphingolipids; D014157:Transcription Factors; D029961:Zebrafish Proteins; D010088:Oxidoreductases; C108138:dihydroceramide desaturase