title: Discrete levels of Twist activity are required to direct distinct cell functions during gastrulation and somatic myogenesis.
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.
authors.affiliation: Program in Developmental Biology, Sloan-Kettering Institute, New York, New York, United States of America; Weill Graduate School at Cornell Medical School, New York, New York, United States of America.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Wong
authors.affiliation: Program in Developmental Biology, Sloan-Kettering Institute, New York, New York, United States of America.
authors.forename: Krista C
authors.initials: KC
authors.lastname: Dobi
authors.affiliation: Program in Developmental Biology, Sloan-Kettering Institute, New York, New York, United States of America; Weill Graduate School at Cornell Medical School, New York, New York, United States of America.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Baylies
mesh_terms: D000483:Alleles; D000818:Animals; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D054262:Gastrulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1