Loss of the ecdysteroid-inducible E75A orphan nuclear receptor uncouples molting from metamorphosis in Drosophila.
Isoform-specific null mutations were used to define the functions of three orphan members of the nuclear receptor superfamily, E75A, E75B, and E75C, encoded by the E75 early ecdysteroid-inducible gene. E75B mutants are viable and fertile, while E75C mutants die as adults. In contrast, E75A mutants have a reduced ecdysteroid titer during larval development, resulting in developmental delays, developmental arrests, and molting defects. Remarkably, some E75A mutant second instar larvae display a heterochronic phenotype in which they induce genes specific to the third instar and pupariate without undergoing a molt. We propose that ecdysteroid-induced E75A expression defines a feed-forward pathway that amplifies or maintains the ecdysteroid titer during larval development, ensuring proper temporal progression through the life cycle.
Howard Hughes Medical Institute, Department of Human Genetics, 15 North 2030 East, University of Utah, Salt Lake City 84112, USA.
Michael
M
Bialecki
Alycia
A
Shilton
Caroline
C
Fichtenberg
William A
WA
Segraves
Carl S
CS
Thummel
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D026461:Ecdysteroids / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D051717:Fushi Tarazu Transcription Factors; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005804:Genes, Lethal / Q000235:genetics; D018398:Homeodomain Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000235:genetics*; D018978:Molting / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011679:Pupa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D026461:Ecdysteroids; C060408:Eip74EF protein, Drosophila; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D019476:Insect Proteins; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C497169:ftz protein, Drosophila; C499712:nuclear hormone receptor FTZ-F1, Drosophila; C110602:transcription factor E75, Manduca