RESUMO
The Drosophila homolog of the retinoid X receptor, ultraspiracle (USP), heterodimerizes with the ecdysone receptor (EcR) to form a functional complex that mediates the effects of the steroid molting hormone ecdysone by activating and repressing expression of ecdysone response genes. As with other retinoid X receptor heterodimers, EcR/USP affects gene transcription in a ligand-modulated manner. We used in vivo, cell culture, and biochemical approaches to analyze the functions of two usp alleles, usp(3) and usp(4), which encode stable proteins with defective DNA-binding domains. We observed that USP is able to activate as well as repress the Z1 isoform of the ecdysone-responsive broad complex (BrC-Z1). Activation of BrC-Z1 as well as EcR, itself an ecdysone response gene, can be mediated by both the USP3 and USP4 mutant proteins. USP3 and USP4 also activate an ecdysone-responsive element, hsp27EcRE, in cultured cells. These results differ from the protein null allele, usp(2), which is unable to mediate activation [Schubiger, M. & Truman, J. W. (2000) Development 127, 1151--1159]. BrC-Z1 repression is compromised in all three usp alleles, suggesting that repression involves the association of USP with DNA. Our results distinguish two mechanisms by which USP modulates the properties of EcR: one that involves the USP DNA-binding domain and one that can be achieved solely through the ligand-binding domain. These newly revealed properties of USP might implicate similar properties for retinoid X receptor.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Drosophila/efeitos dos fármacos , Ecdisona/farmacologia , Receptores do Ácido Retinoico/fisiologia , Fatores de Transcrição/fisiologia , Alelos , Animais , Sítios de Ligação , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Drosophila/fisiologia , Proteínas de Drosophila , Receptores do Ácido Retinoico/genética , Receptores de Esteroides/fisiologia , Receptores X de Retinoides , Hormônios Tireóideos/fisiologia , Fatores de Transcrição/genética , Ativação Transcricional , Tretinoína/fisiologiaRESUMO
The dissatisfaction (dsf) gene is necessary for appropriate sexual behavior and sex-specific neural development in both sexes. dsf males are bisexual and mate poorly, while mutant females resist male courtship and fail to lay eggs. Males and females have sex-specific neural abnormalities. We have cloned dsf and rescued both behavioral and neural phenotypes. dsf encodes a nuclear receptor closely related to the vertebrate Tailless proteins and is expressed in both sexes in an extremely limited set of neurons in regions of the brain potentially involved in sexual behavior. Expression of a female transformer cDNA under the control of a dsf enhancer in males leads to dsf-like bisexual behavior.
Assuntos
Proteínas de Drosophila , Drosophila/fisiologia , Neurônios/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Comportamento Sexual Animal , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Bissexualidade , Drosophila/genética , Elementos Facilitadores Genéticos , Feminino , Regulação da Expressão Gênica , Humanos , Larva , Masculino , Dados de Sequência Molecular , Mutagênese Insercional , Fenômenos Fisiológicos do Sistema Nervoso , Proteínas Nucleares/genética , Oviposição , Pupa , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/genética , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
Many of the same genes needed for proper eye and limb development in vertebrates, such as hairy, hedgehog, patched and cyclic AMP-dependent protein kinase A, are responsible for patterning Drosophila imaginal discs, the tissues that will give rise to the adult cuticle structures. This is well demonstrated in the control of morphogenetic furrow movement and differentiation in the eye imaginal disc. We report that ultraspiracle, the gene encoding the Drosophila cognate of the Retinoid X Receptor, is required for normal morphogenetic furrow movement and ommatidial cluster formation. Examination of the expression of genes involved in regulating the furrow suggests that ultraspiracle defines a novel regulatory pathway in eye differentiation.
