Abstract
Twist (Twi), a conserved basic helix-loop-helix transcriptional regulator, directs the epithelial-to-mesenchymal transition (EMT), and regulates changes in cell fate, cell polarity, cell division and cell migration in organisms from flies to humans. Analogous to its role in EMT, Twist has been implicated in metastasis in numerous cancer types, including breast, pancreatic and prostate. In the Drosophila embryo, Twist is essential for discrete events in gastrulation and mesodermal patterning. In this study, we derive a twi allelic series by examining the various cellular events required for gastrulation in Drosophila. By genetically manipulating the levels of Twi activity during gastrulation, we find that coordination of cell division is the most sensitive cellular event, whereas changes in cell shape are the least sensitive. Strikingly, we show that by increasing levels of Snail expression in a severe twi hypomorphic allelic background, but not a twi null background, we can reconstitute gastrulation and produce viable adult flies. Our results demonstrate that the level of Twi activity determines whether the cellular events of ventral furrow formation, EMT, cell division and mesodermal migration occur.
Highlights
During development, cells are required to proliferate, differentiate and migrate at precise moments to achieve a functional organ or organism
Our analyses show that coordinated cell division can be perturbed in the weakest allelic background, while the process of cell shape change is altered in only the strongest allelic combination
Because mesoderm patterning and somatic myogenesis are sensitive to the level of Twi activity [40], the final somatic muscle pattern of the allelic combinations was first analyzed
Summary
Cells are required to proliferate, differentiate and migrate at precise moments to achieve a functional organ or organism. Regulation of gene expression at the level of transcription has proven to be a key mechanism to coordinate such cellular functions [1,2,3]; it remains an open question how a single transcription factor can coordinate multiple cellular events. The conserved basic helix-loop-helix transcriptional regulator Twist (Twi) is a transcription factor with multiple roles within one tissue throughout development [4]. Twi expression in adult muscle progenitors is required to regulate proliferation and maintain pluripotency until the onset of adult myogenesis [5]. Integral to its role in these processes, Twi activity is required for myriad discrete cell behaviors, but the mechanisms by which Twi exerts this pleiotropic control are unclear
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