title: Mis-specified cells die by an active gene-directed process, and inhibition of this death results in cell fate transformation in Drosophila.
abstract: Incorrectly specified or mis-specified cells often undergo cell death or are transformed to adopt a different cell fate during development. The underlying cause for this distinction is largely unknown. In many developmental mutants in Drosophila, large numbers of mis-specified cells die synchronously, providing a convenient model for analysis of this phenomenon. The maternal mutant bicoid is particularly useful model with which to address this issue because its mutant phenotype is a combination of both transformation of tissue (acron to telson) and cell death in the presumptive head and thorax regions. We show that a subset of these mis-specified cells die through an active gene-directed process involving transcriptional upregulation of the cell death inducer hid. Upregulation of hid also occurs in oskar mutants and other segmentation mutants. In hid bicoid double mutants, mis-specified cells in the presumptive head and thorax survive and continue to develop, but they are transformed to adopt a different cell fate. We provide evidence that the terminal torso signaling pathway protects the mis-specified telson tissue in bicoid mutants from hid-induced cell death, whereas mis-specified cells in the head and thorax die, presumably because equivalent survival signals are lacking. These data support a model whereby mis-specification can be tolerated if a survival pathway is provided, resulting in cellular transformation.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Department of Biochemistry and Molecular Biology, 1515 Holcombe Boulevard, Unit 1000, Houston, TX 77030, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Werz
authors.forename: Tom V
authors.initials: TV
authors.lastname: Lee
authors.forename: Peter L
authors.initials: PL
authors.lastname: Lee
authors.forename: Melinda
authors.initials: M
authors.lastname: Lackey
authors.forename: Clare
authors.initials: C
authors.lastname: Bolduc
authors.forename: David S
authors.initials: DS
authors.lastname: Stein
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D019521:Body Patterning; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D018398:Homeodomain Proteins; D009479:Neuropeptides; D015534:Trans-Activators; C056478:bcd protein, Drosophila; C091675:osk protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila; D020169:Caspases