PUBLICATION

Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling

Authors
Troll, J.V., Hamilton, M.K., Abel, M.L., Ganz, J., Bates, J.M., Stephens, W.Z., Melancon, E., van der Vaart, M., Meijer, A.H., Distel, M., Eisen, J.S., Guillemin, K.
ID
ZDB-PUB-180225-2
Date
2018
Source
Development (Cambridge, England)   145(4): (Journal)
Registered Authors
Bates, Jennifer M., Distel, Martin, Eisen, Judith S., Ganz, Julia, Guillemin, Karen, Meijer, Annemarie H., Stephen, W. Zac, van der Vaart, Michiel
Keywords
Intestinal cell determination, Microbiota, Myd88, Notch, Secretory cell, Zebrafish
MeSH Terms
  • Animals
  • Intestinal Mucosa/metabolism*
  • Intestinal Mucosa/microbiology
  • Intestinal Mucosa/physiology
  • Microbiota*
  • Myeloid Differentiation Factor 88/metabolism*
  • Receptors, Notch/metabolism*
  • Signal Transduction/physiology
  • Zebrafish/metabolism
PubMed
29475973 Full text @ Development
Abstract
Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping