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1.
Nat Cell Biol ; 16(11): 1035-44, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25344753

RESUMEN

Animal development fundamentally relies on the precise control, in space and time, of genome expression. Whereas we have a wealth of information about spatial patterning, the mechanisms underlying temporal control remain poorly understood. Here we show that Pri peptides, encoded by small open reading frames, are direct mediators of the steroid hormone ecdysone for the timing of developmental programs in Drosophila. We identify a previously uncharacterized enzyme of ecdysone biosynthesis, GstE14, and find that ecdysone triggers pri expression to define the onset of epidermal trichome development, through post-translational control of the Shavenbaby transcription factor. We show that manipulating pri expression is sufficient to either put on hold or induce premature differentiation of trichomes. Furthermore, we find that ecdysone-dependent regulation of pri is not restricted to epidermis and occurs over various tissues and times. Together, these findings provide a molecular framework to explain how systemic hormonal control coordinates specific programs of differentiation with developmental timing.


Asunto(s)
Arrestinas/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Ecdisona/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Glutatión Transferasa/metabolismo , Receptores de Esteroides/metabolismo , Animales , Arrestinas/genética , Diferenciación Celular/genética , Proteínas de Drosophila/genética , Ecdisona/genética , Glutatión Transferasa/genética , Mutación/genética , Receptores de Esteroides/genética , Transducción de Señal/fisiología , Transaldolasa/genética , Transaldolasa/metabolismo
2.
Genome Biol ; 14(8): R86, 2013 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-23972280

RESUMEN

BACKGROUND: Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes. RESULTS: We defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome cells. Coupling computational modeling to functional dissection, we investigated the regulatory logic of these enhancers. Extending the repertoire of epidermal effectors using genome-wide approaches showed that the regulatory models learned from this first sample are representative of the whole set of trichome enhancers. These enhancers harbor remarkable features with respect to their functional architectures, including a weak or non-existent clustering of Svb binding sites. The in vivo function of each site relies on its intimate context, notably the flanking nucleotides. Two additional cis-regulatory motifs, present in a broad diversity of composition and positioning among trichome enhancers, critically contribute to enhancer activity. CONCLUSIONS: Our results show that Svb directly regulates a large set of terminal effectors of the remodeling of epidermal cells. Further, these data reveal that trichome formation is underpinned by unexpectedly diverse modes of regulation, providing fresh insights into the functional architecture of enhancers governing a terminal differentiation program.


Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Elementos de Facilitación Genéticos , Regulación del Desarrollo de la Expresión Génica , Genoma , Factores de Transcripción/genética , Tricomas/genética , Animales , Sitios de Unión , Biología Computacional , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Embrión no Mamífero , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Motivos de Nucleótidos , Unión Proteica , Factores de Transcripción/metabolismo , Tricomas/crecimiento & desarrollo , Tricomas/metabolismo
3.
Dev Cell ; 18(1): 64-76, 2010 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-20152178

RESUMEN

The zona pellucida domain (ZPD) defines a conserved family of membrane-anchored matrix proteins that are, as yet, poorly characterized with respect to their functions during development. Using genetic approaches in flies, we show here that a set of eight ZPD proteins is required for the localized reorganization of embryonic epidermal cells during morphogenesis. Despite varying degrees of sequence conservation, these ZPD proteins exert specific and nonredundant functions in the remodeling of epidermal cell shape. Each one accumulates in a restricted subregion of the apical compartment, where it organizes local interactions between the membrane and the extracellular matrix. In addition, ZPD proteins are required to sculpture the actin-rich cell extensions and maintain appropriate organization of the apical compartment. These results on ZPD proteins therefore reveal a functional subcompartmentalization of the apical membrane and its role in the polarized control of epithelial cell shape during development.


Asunto(s)
Drosophila melanogaster/embriología , Drosophila melanogaster/metabolismo , Proteínas del Huevo/metabolismo , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , Células Epiteliales/metabolismo , Citoesqueleto de Actina/metabolismo , Animales , Compartimento Celular/fisiología , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Polaridad Celular/fisiología , Forma de la Célula/fisiología , Extensiones de la Superficie Celular/metabolismo , Extensiones de la Superficie Celular/ultraestructura , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Proteínas del Huevo/genética , Embrión no Mamífero/citología , Desarrollo Embrionario/fisiología , Células Epidérmicas , Epidermis/metabolismo , Células Epiteliales/citología , Matriz Extracelular/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Estructura Terciaria de Proteína/fisiología
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