A re-inducible gap gene cascade patterns the anterior-posterior axis of insects in a threshold-free fashion

Abstract

Gap genes mediate the division of the anterior-posterior axis of insects into different fates through regulating downstream hox genes. Decades of tinkering the segmentation gene network of the long-germ fruit fly Drosophila melanogaster led to the conclusion that gap genes are regulated (at least initially) through a threshold-based French Flag model, guided by both anteriorly-and posteriorly-localized morphogen gradients. In this paper, we show that the expression patterns of gap genes in the intermediate-germ beetle Tribolium castaneum are mediated by a threshold-free 'Speed Regulation' mechanism, in which the speed of a genetic cascade of gap genes is regulated by a posterior gradient of the transcription factor Caudal. We show this by re-inducing the leading gap gene (namely, hunchback) resulting in the re-induction of the gap gene cascade at arbitrary points in time. This demonstrates that the gap gene network is self-regulatory and is primarily under the control of a posterior speed regulator in Tribolium and possibly all insects.

Speeding up anterior-posterior patterning of insects by differential initialization of the gap gene cascade

“…Thus, a patterning mechanism based on the speed regulation of a genetic cascade by a posterior-toanterior morphogen (like that hypothesized for ancestral insects) can smoothly evolve into a simultaneous patterning mechanism based (possibly solely) on an anterior-to-posterior gradient of the first gene in the cascade. In refs (10,45), we provided evidence that patterning the AP axis of Tribolium is based on the former mechanism. Here we argue that patterning the AP axis of Drosophila is (partially) based on the latter mechanism.…”

“…Depleting caudal (cad) transcripts by RNAi completely abolishes trunk gap gene expressions. Furthermore, the gap gene cascade can be re-induced in the cad-expressing posterior end of the embryo in the germband stage, where the influence of anterior-to-posterior gradients is unlikely (45). On the other hand, the gap gene system in Drosophila is heavily dependent on anterior-to-posterior morphogen gradients (namely, Bicoid and maternal Hb) and is less dependent on the posterior-to-anterior gradient of Cad (24,25,46,47).…”

Patterning with clocks and genetic cascades: Segmentation and regionalization of vertebrate versus insect body plans

“…A similar model was suggested for gap gene regulation in Tribolium (replacing the clock with a genetic cascade). In line with this model, reactivating the gap gene hb all over the embryo resulted in 2 distinct responses [ 201 ]. Within the Wnt/Cad expression (defining the SAZ), the gap genetic cascade was reset, and the whole gap gene sequence was reproduced.…”

“…The maternal Hb gradient, however, plays less prominent role in Tribolium : Flattening the maternal Hb gradient in Tribolium (by knocking down nos ; pum ) only slows down the onset of the sequential activation of gap genes [ 9 ]. Alternatively, the posterior-to-anterior gradient of Wnt/Cad was proposed to be a master regulator of gap genes in Tribolium [ 3 , 201 ]. Depleting cad by RNAi completely abolishes gap gene expressions in Tribolium , and manipulating the Wnt/Cad gradient in several genetic backgrounds leads to stereotypical changes in the spatiotemporal dynamics of gap gene expression waves similar to those observed for pair-rule genes in the same genetic backgrounds [ 3 , 8 ].…”

Time and space in segmentation

“…Hox and gap gene expression is activated by posterior factors such as Cdx and Wnt [15,161–164], and the individual genes also cross-regulate each other’s expression. Thus Hox and gap gene expression depends partly on the state of the SAZ and partly on intrinsic dynamics [57,165–167]. As well as generating regionalization information, the sequential expression of these genes affects segment patterning, via effects on SAZ maintenance and axial elongation [78,168–171].…”