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 embryonic dorsal-ventral axis, we used two light-inducible tags that result in either nuclear export or degradation of Dorsal when exposed to blue light. Nuclear export of Dorsal results in loss of expression for the high threshold, ventrally-expressed target gene () but retention of the low threshold, laterally-expressed target gene (). In contrast, degradation of Dorsal results in retention of loss of , and lower nuclear levels than when Dorsal is exported from the nucleus. To elucidate how nuclear export results in loss of but degradation does not, we investigated Dorsal kinetics using photobleaching and found it reenters the nucleus even under conditions of blue-light when export is favored. The associated kinetics of being imported and exported continuously are likely responsible for loss of but, alternatively, can support . Collectively, our results show that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.
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http://dx.doi.org/10.1101/2024.05.20.595009 | DOI Listing |
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Department of Pharmacology, Shaanxi University of Chinese Medicine, No. 1 Middle Section of Century Avenue, Xianyang 712046, People's Republic of China. Electronic address:
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Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Sector-125, Noida 201313, Uttar Pradesh, India. Electronic address:
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Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Colon cancer remains a significant health burden globally, necessitating deeper investigation. Identification and targeting of prognostic markers can significantly improve the current therapeutic approaches for colon cancer. The differential nuclear transport (import and export) of cellular proteins, plays an important role in tumor progression.
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Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Therapeutic nucleic acids (TNAs) including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) have emerged as promising treatment strategies for a wide variety of diseases, offering the potential to modulate gene expression with a high degree of specificity. These small, synthetic nucleic acid-like molecules provide unique advantages over traditional pharmacological agents, including the ability to target previously "undruggable" genes. Despite this promise, several biological barriers severely limit their clinical efficacy.
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