Journal
GENES & DEVELOPMENT
Volume 17, Issue 24, Pages 3100-3111Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1160803
Keywords
HLH-2; LIN-12; Notch; birth order; LAG-2; Delta
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Funding
- NCI NIH HHS [CA 095389, R01 CA095389] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007088, GM 07088] Funding Source: Medline
- NINDS NIH HHS [NS 35556] Funding Source: Medline
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The anchor cell/ventral uterine precursor cell (AC/VU) decision in Caenorhabditis elegans is a canonical example of lin-12/Notch-mediated lateral specification. Two initially equivalent cells interact via the receptor LIN-12 and its ligand LAG-2, so that one becomes the AC and the other a VU. During this interaction, feedback loops amplify a small difference in lin-12 activity, limiting lin-12 transcription to the presumptive VU and lag-2 transcription to the presumptive AC. Here, we find that hlh-2 appears to be required for the VU fate and directly activates lag-2 transcription in the presumptive AC. HLH-2 appears to accumulate selectively in the presumptive AC prior to differential transcription of lin-12 or lag-2, and is therefore the earliest detectable difference between the two cells undergoing the AC/VU decision. The restricted accumulation of HLH-2 to the presumptive AC reflects post-transcriptional down-regulation of HLH-2 in the presumptive VU. Our observations suggest that hlh-2 is regulated as part of the negative feedback that down-regulates lag-2 transcription in the presumptive VU. Finally, we show that the AC/VU decision in an individual hermaphrodite is biased by the relative birth order of the two cells, so that the first-born cell is more likely to become the VU. We propose models to suggest how birth order, HLH-2 accumulation, and transcription of lag-2 may be linked during the AC/VU decision.
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