The decapentaplegic Core Promoter Region Plays an Integral Role in the Spatial Control of Transcription

Abstract

The Drosophila melanogaster decapentaplegic (dpp) gene encodes a transforming growth factor ␤-related cell signaling molecule that plays a critical role in dorsal/ventral pattern formation. The dpp expression pattern in the Drosophila embryo is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, phases II and III, in which dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III), depend on multiple independent elements in the dpp 5-flanking region. Several aspects of the normal dpp expression pattern appear to depend on the unique properties of the dpp core promoter. For example, this core promoter (extending from ؊22 to ؉6) is able to direct a phase II expression pattern in the absence of additional upstream or downstream regulatory elements. In addition, a ventral-specific enhancer in the dpp 5-flanking region that binds the Dorsal factor activates the heterologous hsp70 core promoter but not the dpp core promoter. Thus, the dpp core promoter region may contribute to spatially regulated transcription both by interacting directly with spatially restricted activators and by modifying the activity of proteins bound to enhancer elements.The transforming growth factor ␤ gene superfamily encodes a large set of cell signaling proteins with diverse roles in development, cell growth, and differentiation (21). These factors are synthesized as long precursors, which are processed to generate ϳ100-amino-acid polypeptide factors. The signals generated by these secreted factors are transmitted by membrane-bound receptor serine/threonine kinases (22). Because several members of the transforming growth factor ␤ superfamily contribute to spatially regulated developmental phenomena, a full understanding of the processes that are controlled by these factors will require an understanding of the mechanisms that control their spatially restricted synthesis and release.The product of the decapentaplegic (dpp) gene is one of several known transforming growth factor ␤-related factors in Drosophila melanogaster (23). Among its many roles in both embryonic and larval development, Dpp acts as a morphogen that helps to determine cell fate on the dorsal side of the embryo (8). The expression pattern of dpp in the developing embryo is controlled at the level of transcription and is extremely dynamic, consisting of three distinct phases (30). In phase I expression, which is first detected in the syncytial blastoderm (ϳ1.5 h postfertilization), dpp is transcribed in the dorsal 40% of the embryo, a region that includes the anlagen of the amnioserosa and the dorsal epidermis ( Fig. 1A and D). Phase I expression is dependent upon the maternally encoded Dorsal morphogen, which binds to elements in the dpp second intron to repress dpp expression in the ventral 60% of the blastoderm embryo (13)....

Bone morphogenetic proteins: multifunctional regulators of vertebrate development.

“…In the blastoderm embryo, for example, dpp is re pressed by Dorsal, a transcription factor related to NF-KB (Schwyter et al 1995). In the midgut, dpp is regulated positively and negatively by the homeo domain proteins, Ultrabithorax (Ubx) and Abdominal-A [Abd-A), respec tively, and DNA sequences required for direct activation by Ubx have been identified (Bienz 1994;Capovilla et al 1994).…”

Drosophila Jun kinase regulates expression of decapentaplegic via the ETS-domain protein Aop and the AP-1 transcription factor DJun during dorsal closure.

“…dpp expression during the later stages of embryogenesis, when dorsal closure occurs, has been referred to as phase III expression. An -500-bp enhancer fragment located 400-bp upstream of the transcription start site is necessary and sufficient for dpp ectodermal phase III expression (Schwyter et al 1995). DJun and Aop may regu- Riesgo-Escovar et al 1996), DJNK is activated (DJNK aCt) and translocates into the nucleus, where it phosphorylates Aop and DJun (B).…”

“…and its expression is dependent of DJNK and DJNKK function (Glise et al 1995;Riesgo-Escovar et al 1996). Whereas expression of puc at this stage is restricted to the leading edge cells, dpp is expressed in a highly dynamic pattern in other cells as well Schwyter et al 1995). To test whether dpp expression is also controlled by DJNK activity, we examined its expression in embryos with reduced maternal and zygotic bsk function.…”

The TGF-β Family: Signaling Pathways, Developmental Roles, and Tumor Suppressor Activities

“…Three regions, each containing distinct cis-regulatory sequences, have been identified at the dpp locus. Reporter gene studies utilizing enhancer elements from each of these regions [11,12,13] have shown that discrete cis-regulatory elements are sufficient to direct dpp expression in subsets of its normal expression pattern. Reporter gene studies in mice of two TGF-β family members, BMP2 (a dpp homologue) and Nodal, have given similar results [14,15].…”