High impact information on twi

• To initiate the differentiation of the mesoderm in Drosophila, multiple zygotic genes such as twist (twi) and snail (sna), which encode a basic-helix-loop-helix and a zinc finger transcription factor, respectively, are required [1].
• This is explained by results showing that dCBP is necessary for dl-mediated activation of the twi promoter [1].
• The transcription factor Twist initiates Drosophila mesoderm development, resulting in the formation of heart, somatic muscle, and other cell types [2].
• Altering amounts of Twist after gastrulation revealed that high levels of Twist are required for somatic myogenesis and block the formation of other mesodermal derivatives [3].
• The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently excluded from the myotome [4].

Biological context of twi

• Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset [5].
• Transgenes misexpressing Pelle and Twist were introduced into different mutant backgrounds and the patterning activities were visualized using various target genes that respond to different thresholds of Toll-Dorsal signaling [5].
• A two-step procedure in which maternally expressed sequences were subtracted from each of these cDNA libraries, before subtracting twi from wild-type, increased the subtraction efficiency [6].
• Here we show that Dorsal and the bHLH activator Twist synergistically activate transcription in cell culture and in vitro from a promoter containing binding sites for both factors [7].
• Nonetheless, the regions of Twist and Dorsal required for the binding interaction are also required for synergistic transcriptional activation [7].

Anatomical context of twi

• Two zygotic genes, snail (sna) and twist (twi), are required for mesoderm development, which begins with the formation of the ventral furrow [8].
• Both twi and sna are expressed ventrally in the blastoderm, encode transcription factors and promote the invagination of the ventral furrow by activating or repressing appropriate target genes [8].
• In the third instars discs, in the vicinity of tendon progenitors, some Twist-positive myoblasts start to express the muscle founder cell marker dumbfounded (duf) [9].
• It is novel and its expression is mesoderm-specific, twi-dependent, and early during somatic, visceral, and heart muscle differentiation [6].
• High Twist levels direct cells to the body wall muscle fate, whereas low levels are permissive for gut muscle and fat body fate [10].

Physical interactions of twi

• Using a combination of promoter fusion-P-transformation assays, and in vitro DNA-binding assays coupled with site-directed mutagenesis, we establish a direct link between dl-binding sites and twi expression in the early embryo [11].

Regulatory relationships of twi

• The expression of wntD is activated by Dorsal and Twist, but the expression is much reduced in the ventral cells through repression by Snail [12].
• We show that Su(H)-mediated Notch signaling represses Twist expression during subdivision and thus plays a critical role in patterning mesodermal segments [10].
• We present evidence that dl and twi directly activate sna expression [13].
• We provide evidence that ap ectopic expression can induce per se ectopic twi expression and muscle degeneration [14].
• Dip3 functions as a coactivator to stimulate synergistic activation by Dorsal and Twist, but does not stimulate simple activation of promoters containing only Dorsal or only Twist binding sites [15].

Other interactions of twi

• In the anterior part, hkb antagonizes the activation of target genes by twi and sna [8].
• We investigate the activities of the Pelle kinase and Twist basic helix-loop-helix (bHLH) transcription factor in transducing Toll signaling [5].
• We discuss how the Dorsal gradient system can be modified during metazoan evolution and conclude that Dorsal-Twist interactions are distinct from the interplay between Bicoid and Hunchback, which pattern the anteroposterior axis [5].
• Our work demonstrates that Notch acts as a transcriptional switch on mesodermal target genes, and it suggests that Notch/Su(H) directly regulates twist, as well as indirectly regulating twist by activating proteins that repress Twist [10].
• The combination of a common set of mesoderm autonomous transcription factors (e.g. Tinman and Twist) and spatially restricted inductive signals (e.g. Dpp and Wg) subdivide the dorsal mesoderm into different competence domains [16].

Analytical, diagnostic and therapeutic context of twi

• During Drosophila gastrulation, apical constrictions under the control of the transcription factor Twist lead to the invagination of the mesoderm [17].

References