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

TY - JOUR

T1 - Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

AU - Serup, Palle

AU - Gustavsen, Carsten

AU - Klein, Tino

AU - Potter, Leah A

AU - Lin, Robert

AU - Mullapudi, Nandita

AU - Wandzioch, Ewa

AU - Hines, Angela

AU - Davis, Ashley

AU - Bruun, Christine

AU - Engberg, Nina

AU - Petersen, Dorthe R

AU - Peterslund, Janny M L

AU - Macdonald, Raymond J

AU - Grapin-Botton, Anne

AU - Magnuson, Mark A

AU - Zaret, Kenneth S

PY - 2012/11/1

Y1 - 2012/11/1

N2 - 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.

AB - 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.

U2 - 10.1242/dmm.009696

DO - 10.1242/dmm.009696

M3 - Journal article

C2 - 22888097

SN - 1754-8403

VL - 5

SP - 956

EP - 966

JO - Disease Models & Mechanisms

JF - Disease Models & Mechanisms

IS - 6

ER -