Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation

Defining the time of action for morphogens requires tools capable of temporally controlled perturbations. To study how the transcription factor Dorsal affects patterning of the Drosophila embryonic dorsal-ventral axis, we used two light-inducible tags that trigger either nuclear export or degradation of Dorsal under blue light. Nuclear export of Dorsal leads to loss of the high-threshold, ventrally expressed target gene snail (sna), while the low-threshold, laterally expressed target gene short-gastrulation (sog) is retained. In contrast, degradation of Dorsal results in retention of sna, loss of sog, and lower nuclear levels compared to when Dorsal is exported from the nucleus. To understand why nuclear export causes loss of sna but degradation does not, we investigated Dorsal kinetics using photobleaching and found that it rapidly re-enters the nucleus even under blue-light conditions favoring export. The associated kinetics of Dorsal being rapidly imported and exported continuously are likely responsible for loss of sna but, alternatively, can support sog. Collectively, our results indicate that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.

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Publication Details

Journal
Development
Published
2024-10-14
DOI
https://doi.org/10.1242/dev.202775
Citations
2
Primary Topic
Neurobiology and Insect Physiology Research
Type
article
Field-Weighted Citation Impact
0.54

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article

Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation

Angelike Stathopoulos, James McGehee
2 citations
Development
Neurobiology and Insect Physiology Research
0.54
article

Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation

Angelike Stathopoulos, James McGehee
article en
2 citations

Abstract

Defining the time of action for morphogens requires tools capable of temporally controlled perturbations. To study how the transcription factor Dorsal affects patterning of the Drosophila embryonic dorsal-ventral axis, we used two light-inducible tags that trigger either nuclear export or degradation of Dorsal under blue light. Nuclear export of Dorsal leads to loss of the high-threshold, ventrally expressed target gene snail (sna), while the low-threshold, laterally expressed target gene short-gastrulation (sog) is retained. In contrast, degradation of Dorsal results in retention of sna, loss of sog, and lower nuclear levels compared to when Dorsal is exported from the nucleus. To understand why nuclear export causes loss of sna but degradation does not, we investigated Dorsal kinetics using photobleaching and found that it rapidly re-enters the nucleus even under blue-light conditions favoring export. The associated kinetics of Dorsal being rapidly imported and exported continuously are likely responsible for loss of sna but, alternatively, can support sog. Collectively, our results indicate that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.

DevelopmentVol. 151(21)
California Institute of Technology (US)
California Institute of Technology, National Institutes of Health
Openalex Percentile: Top 35%
Neurobiology and Insect Physiology Research
0.54
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