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 Drosophila melanogaster led to the conclusion that gap genes are regulated (at least initially) through a threshold-based mechanism, guided by both anteriorly- and posteriorly-localized morphogen gradients. In this paper, we show that the response of the gap gene network in the beetle Tribolium castaneum upon perturbation is consistent with a threshold-free ‘Speed Regulation’ mechanism, in which the speed of a genetic cascade of gap genes is regulated by a posterior morphogen gradient. 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 regulator in Tribolium and possibly other short/intermediate-germ insects.

Arthropod segmentation

“…Gap genes appear to play some role in controlling the duration of segment addition (Cerny et al, 2005;Nakao, 2016). Over time, gap genes are expressed sequentially within the SAZ, their turnover driven by cross-regulatory interactions (Boos et al, 2018;Verd et al, 2018). This process, effectively a developmental 'timer', shows intriguing similarities to the 'neuroblast clock' (Isshiki et al, 2001;Peel et al, 2005).…”

“…This process, effectively a developmental 'timer', shows intriguing similarities to the 'neuroblast clock' (Isshiki et al, 2001;Peel et al, 2005). It evidently exerts some control over the body plan, as perturbing hunchback expression can both decrease (Liu and Kaufman, 2004;Marques-Souza et al, 2008;Mito et al, 2005) and increase (Boos et al, 2018;Nakao, 2016) segment number in sequentially segmenting insects. These phenotypes are not well understood, but might result from gap genes directly or indirectly regulating cell behaviour within the SAZ.…”

The mlpt/Ubr3/Svb module comprises an ancient developmental switch for embryonic patterning

“…In beetles, RNAi knockdown of mlpt caused posterior truncation of the embryo, with a loss of abdominal segments, as well as the transformation of remaining anterior abdominal segments to thoracic fate, leading to a distinctive phenotype of extra pairs of legs (mille-pattes is French for centipede). Additional work established that mlpt acts as a gap gene in Tribolium ( Boos et al, 2018 ; Ribeiro et al, 2017 ; Savard et al, 2006 ; van der Zee et al, 2006 ; Zhu et al, 2017 ), where more limited homeotic transformations often accompany loss of gap gene function ( Bucher and Klingler, 2004 ; Cerny et al, 2005 ; Marques-Souza et al, 2008 ). Unlike Drosophila which has evolved a derived mode of segmentation (called ‘long germ’) in which all segments are formed nearly simultaneously in the syncytial environment of the blastoderm, Tribolium is more representative of the ancestral mode of segmentation in insects ( Peel et al, 2005 ).…”

Time and space in segmentation

“…Hox and gap gene expression is activated by posterior factors such as Cdx and Wnt [15,[161][162][163][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][166][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][169][170][171].…”