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.
Bialecki
Michael
M
Howard Hughes Medical Institute, Department of Human Genetics, 15 North 2030 East, University of Utah, Salt Lake City 84112, USA.
Shilton
Alycia
A
Fichtenberg
Caroline
C
Segraves
William A
WA
Thummel
Carl S
CS
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