Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

Palle Serup, Carsten Gustavsen, Tino Klein, Leah A. Potter, Robert Lin, Nandita Mullapudi, Ewa Wandzioch, Angela Hines, Ashley Davis, Christine Bruun, Nina Engberg, Dorthe R. Petersen, Janny M L Peterslund, Raymond J. MacDonald, Anne Grapin-Botton, Mark A. Magnuson, Kenneth S. Zaret

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE) to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements.

Original languageEnglish (US)
Pages (from-to)956-966
Number of pages11
JournalDMM Disease Models and Mechanisms
Volume5
Issue number6
DOIs
StatePublished - Nov 2012

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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