A damped oscillator imposes temporal order on posterior gap gene expression inDrosophila

AbstractInsects determine their body segments in two different ways. Short-germband insects, such as the flour beetleTribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar flyDrosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of theDrosophilasegmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of theDrosophilaembryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. InTribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels inDrosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition, and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.Author summaryDifferent insect species exhibit one of two distinct modes of determining their body segments during development: they either use a molecular oscillator to position segments sequentially, or they generate segments simultaneously through a hierarchical gene-regulatory cascade. The sequential mode is ancestral, while the simultaneous mode has been derived from it independently several times during evolution. In this paper, we present evidence which suggests that simultaneous segmentation also involves an oscillator in the posterior of the embryo of the vinegar fly,Drosophila melanogaster. This surprising result indicates that both modes of segment determination are much more similar than previously thought. Such similarity provides an important step towards explaining the frequent evolutionary transitions between sequential and simultaneous segmentation.

Download Full-text

tarsal-less is expressed as a gap gene but has no gap gene phenotype in the moth midge Clogmia albipunctata

Royal Society Open Science ◽

10.1098/rsos.180458 ◽

2018 ◽

Vol 5 (8) ◽

pp. 180458 ◽

Cited By ~ 2

Author(s):

Eva Jiménez-Guri ◽

Karl R. Wotton ◽

Johannes Jaeger

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Rna Interference ◽

Gap Gene ◽

Gap Genes ◽

Subtle Effect ◽

Bona Fide ◽

Vinegar Fly ◽

Clogmia Albipunctata ◽

Overlapping Domains

Gap genes are involved in segment determination during early development of the vinegar fly Drosophila melanogaster and other dipteran insects (flies, midges and mosquitoes). They are expressed in overlapping domains along the antero-posterior (A–P) axis of the blastoderm embryo. While gap domains cover the entire length of the A–P axis in Drosophila, there is a region in the blastoderm of the moth midge Clogmia albipunctata , which lacks canonical gap gene expression. Is a non-canonical gap gene functioning in this area? Here, we characterize tarsal-less ( tal ) in C. albipunctata . The homologue of tal in the flour beetle Tribolium castaneum (called milles-pattes, mlpt ) is a bona fide gap gene. We find that Ca-tal is expressed in the region previously reported as lacking gap gene expression. Using RNA interference, we study the interaction of Ca-tal with gap genes. We show that Ca-tal is regulated by gap genes, but only has a very subtle effect on tailless (Ca-tll), while not affecting other gap genes at all. Moreover, cuticle phenotypes of Ca-tal depleted embryos do not show any gap phenotype. We conclude that Ca-tal is expressed and regulated like a gap gene, but does not function as a gap gene in C. albipunctata .

Download Full-text

tarsal-less is expressed as a gap gene but has no gap gene phenotype in the moth midge Clogmia albipunctata

10.1101/266288 ◽

2018 ◽

Author(s):

Eva Jiménez-Guri ◽

Karl R. Wotton ◽

Johannes Jaeger

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Rna Interference ◽

Gap Gene ◽

Gap Genes ◽

Subtle Effect ◽

Bona Fide ◽

Vinegar Fly ◽

Clogmia Albipunctata ◽

Overlapping Domains

AbstractGap genes are involved in segment determination during early development of the vinegar fly Drosophila melanogaster and other dipteran insects (flies, midges, and mosquitoes). They are expressed in overlapping domains along the antero-posterior (A–P) axis of the blastoderm embryo. While gap domains cover the entire length of the A–P axis in Drosophila, there is a region in the blastoderm of the moth midge Clogmia albipunctata, which lacks canonical gap gene expression. Is a non-canonical gap gene functioning in this area? Here, we characterize tarsal-less (tal) in C. albipunctata. The homolog of tal in the flour beetle Tribolium castaneum (called milles-pattes, mlpt) is a bona fide gap gene. We find that Ca-tal is expressed in the region previously reported as lacking gap gene expression. Using RNA interference, we study the interaction of Ca-tal with gap genes. We show that Ca-tal is regulated by gap genes, but only has a very subtle effect on tailless (Catll), while not affecting other gap genes at all. Moreover, cuticle phenotypes of Ca-tal depleted embryos do not show any gap phenotype. We conclude that Ca-tal is expressed and regulated like a gap gene, but does not function as a gap gene in C. albipunctata.

Download Full-text

The neuroblast timer gene nubbin exhibits functional redundancy with gap genes to regulate segment identity in Tribolium

10.1101/2021.04.08.438913 ◽

2021 ◽

Author(s):

Olivia R A Tidswell ◽

Matthew A Benton ◽

Michael E Akam

Keyword(s):

Gene Expression ◽

Regulatory Network ◽

Gene Network ◽

In Situ Hybridisation ◽

Hox Gene ◽

Gap Gene ◽

Gap Genes ◽

Sequential Mode ◽

And Function

In Drosophila, segmentation genes of the gap class form a regulatory network that positions segment boundaries and assigns segment identities. This gene network shows striking parallels with another gene network known as the neuroblast timer series. The neuroblast timer genes hunchback, Krüppel, nubbin, and castor are expressed in temporal sequence in neural stem cells to regulate the fate of their progeny. These same four genes are expressed in corresponding spatial sequence along the Drosophila blastoderm. The first two, hunchback and Krüppel, are canonical gap genes, but nubbin and castor have limited or no roles in Drosophila segmentation. Whether nubbin and castor regulate segmentation in insects with the ancestral, sequential mode of segmentation remains largely unexplored. We have investigated the expression and functions of nubbin and castor during segment patterning in the sequentially-segmenting beetle Tribolium. Using multiplex fluorescent in situ hybridisation, we show that Tc-hunchback, Tc-Krüppel, Tc-nubbin and Tc-castor are expressed sequentially in the segment addition zone of Tribolium, in the same order as they are expressed in Drosophila neuroblasts. Furthermore, simultaneous disruption of multiple genes reveals that Tc-nubbin regulates segment identity, but does so redundantly with two previously described gap/gap-like genes, Tc-giant and Tc-knirps. Knockdown of two or more of these genes results in the formation of up to seven pairs of ectopic legs on abdominal segments. We show that this homeotic transformation is caused by loss of abdominal Hox gene expression, likely due to expanded Tc-Krüppel expression. Our findings support the theory that the neuroblast timer series was co-opted for use in insect segment patterning, and contribute to our growing understanding of the evolution and function of the gap gene network outside of Drosophila.

Download Full-text

Gap genes are involved in inviability in hybrids between Drosophila melanogaster and D. santomea

10.1101/2021.12.06.471493 ◽

2021 ◽

Author(s):

Wenhan Chang ◽

Martin Kreitman ◽

Daniel R. Matute

Keyword(s):

Drosophila Melanogaster ◽

Gene Network ◽

Developmental Process ◽

Coding Region ◽

Pure Species ◽

Closely Related Species ◽

Hybrid Inviability ◽

Gap Gene ◽

Gap Genes ◽

Anterior Posterior

ABSTRACTEvolved changes within species lead to the inevitable loss of viability in hybrids. Inviability is also a convenient phenotype to genetically map and validate functionally divergent genes and pathways differentiating closely related species. Here we identify the Drosophila melanogaster form of the highly conserved essential gap gene giant (gt) as a key genetic determinant of hybrid inviability in crosses with D. santomea. We show that the coding region of this allele in D. melanogaster/D. santomea hybrids is sufficient to cause embryonic inviability not seen in either pure species. Further genetic analysis indicates that tailless (tll), another gap gene, is also involved in the hybrid defects. giant and tll are both members of the gap gene network of transcription factors that participate in establishing anterior-posterior specification of the dipteran embryo, a highly conserved developmental process. Genes whose outputs in this process are functionally conserved nevertheless evolve over short timescales to cause inviability in hybrids.

Download Full-text

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

10.1101/485151 ◽

2018 ◽

Author(s):

Heike Rudolf ◽

Christine Zellner ◽

Ezzat El-Sherif

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Fruit Fly ◽

Red Flour Beetle ◽

Evolutionary Transition ◽

Gap Gene ◽

Sequential Mode ◽

Patterning Genes ◽

Computational Analyses ◽

Anterior Posterior

AbstractRecently, it was shown that anterior-posterior patterning genes in the red flour beetle Tribolium castaneum are expressed sequentially in waves. However, in the fruit fly Drosophila melanogaster, an insect with a derived mode of embryogenesis compared to Tribolium, anterior-posterior patterning genes quickly and simultaneously arise as mature gene expression domains that, afterwards, undergo slight posterior-to-anterior shifts. This raises the question of how a fast and simultaneous mode of patterning, like that of Drosophila, could have evolved from a rather slow sequential mode of patterning, like that of Tribolium. In this paper, we elucidate a mechanism for this evolutionary transition based on a switch from a uniform to a gradient-mediated initialization of the gap gene cascade by maternal Hb. The model is supported by computational analyses and experiments.

Download Full-text

An efficient gene regulatory network inference algorithm for early Drosophila melanogaster embryogenesis

10.1101/213025 ◽

2017 ◽

Author(s):

Hirotaka Matsumoto ◽

Hisanori Kiryu ◽

Yasuhiro Kojima ◽

Suguru Yaginuma ◽

Itoshi Nikaido

Keyword(s):

Drosophila Melanogaster ◽

Regulatory Network ◽

Efficient Algorithm ◽

Large Scale ◽

Gap Gene ◽

Large Scale Data ◽

Gap Genes ◽

Simulation Based ◽

Gene Regulatory ◽

Scale Data

AbstractThe spatial patterns of gene expression in early Drosophila melanogaster embryogenesis have been studied experimentally and theoretically to reveal the molecular basis of morphogenesis. In particular, the gene regulatory network (GRN) of gap genes has been investigated through mathematical modeling and simulation. Although these simulation-based approaches are useful for describing complex dynamics and have revealed several important regulations in spatial patterning, they are computationally intensive because they optimize GRN with iterative simulation. Recently, the advance of experimental technologies is enabling the acquisition of comprehensive spatial expression data, and an efficient algorithm will be necessary to analyze such large-scale data. In this research, we developed an efficient algorithm to infer the GRN based on a linear reaction-diffusion model. First, we qualitatively analyzed the GRNs of gap genes and pair-rule genes based on our algorithm and showed that two mutual repressions are fundamental regulations. Then, we inferred the GRN from gap gene data, and identified asymmetric regulations in addition to the two mutual repressions. We analyzed the effect of these asymmetric regulations on spatial patterns, and showed that they have the potential to adjust peak position. Our algorithm runs in sub-second time, which is significantly smaller than the runtime of simulation-based approaches (between 8 and 160 h, for exmaple). Neverthe-less, our inferred GRN was highly correlated with the simulation-based GRNs. We also analyzed the gap gene network of Clogmia albipunctata and showed that different mutual repression regulations might be important in comparison with those of Drosophila melanogaster. As our algorithm can infer GRNs efficiently and can be applied to several different network analysis, it will be a valuable approach for analyzing large-scale data.

Download Full-text

Dynamic Maternal Gradients Control Timing and Shift-Rates forDrosophilaGap Gene Expression

10.1101/068064 ◽

2016 ◽

Author(s):

Berta Verd ◽

Anton Crombach ◽

Johannes Jaeger

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Drosophila Melanogaster ◽

Pattern Formation ◽

Dynamic Process ◽

Gene Expression Pattern ◽

The Body ◽

Transient Dynamics ◽

Gap Gene ◽

Gap Genes

AbstractPattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network inDrosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded bybicoid (bcd)andcaudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.Author SummaryAnimal development is a highly dynamic process. Biochemical or environmental signals can cause the rules that shape it to change over time. We know little about the effects of such changes. For the sake of simplicity, we usually leave them out of our models and experimental assays. Here, we do exactly the opposite. We characterise precisely those aspects of pattern formation caused by changing signalling inputs to a gene regulatory network, the gap gene system ofDrosophila melanogaster. Gap genes are involved in determining the body segments of flies and other insects during early development. Gradients of maternal morphogens activate the expression of the gap genes. These gradients are highly dynamic themselves, as they decay while being read out. We show that this decay controls the peak concentration of gap gene products, produces smooth boundaries of gene expression, and slows down the observed positional shifts of gap domains in the posterior of the embryo, thereby stabilising the spatial pattern. Our analysis demonstrates that the dynamics of gene regulation not only affect the timing, but also the positioning of gene expression. This suggests that we must pay closer attention to transient dynamic aspects of development than is currently the case.

Download Full-text

Needs and Targets for the multi sex combs Gene Product in Drosophila melanogaster

Genetics ◽

10.1093/genetics/149.4.1823 ◽

1998 ◽

Vol 149 (4) ◽

pp. 1823-1838 ◽

Cited By ~ 1

Author(s):

Olivier Saget ◽

Françoise Forquignon ◽

Pedro Santamaria ◽

Neel B Randsholt

Keyword(s):

Drosophila Melanogaster ◽

Ectopic Expression ◽

Polycomb Group ◽

Homeotic Genes ◽

Maternal Control ◽

Gap Gene ◽

Sex Combs ◽

Normal Expression ◽

Selector Genes ◽

Mutant Phenotypes

Abstract We have analyzed the requirements for the multi sex combs (mxc) gene during development to gain further insight into the mechanisms and developmental processes that depend on the important trans-regulators forming the Polycomb group (PcG) in Drosophila melanogaster. mxc is allelic with the tumor suppressor locus lethal (1) malignant blood neoplasm (l(1)mbn). We show that the mxc product is dramatically needed in most tissues because its loss leads to cell death after a few divisions. mxc has also a strong maternal effect. We find that hypomorphic mxc mutations enhance other PcG gene mutant phenotypes and cause ectopic expression of homeotic genes, confirming that PcG products are cooperatively involved in repression of selector genes outside their normal expression domains. We also demonstrate that the mxc product is needed for imaginal head specification, through regulation of the ANT-C gene Deformed. Our analysis reveals that mxc is involved in the maternal control of early zygotic gap gene expression previously reported for some PcG genes and suggests that the mechanism of this early PcG function could be different from the PcG-mediated regulation of homeotic selector genes later in development. We discuss these data in view of the numerous functions of PcG genes during development.

Download Full-text

Posterior stripe expression of hunchback is driven from two promoters by a common enhancer element

Development ◽

10.1242/dev.121.9.3067 ◽

1995 ◽

Vol 121 (9) ◽

pp. 3067-3077 ◽

Cited By ~ 10

Author(s):

J.S. Margolis ◽

M.L. Borowsky ◽

E. Steingrimsson ◽

C.W. Shim ◽

J.A. Lengyel ◽

...

Keyword(s):

Transcription Initiation ◽

Initiation Site ◽

Drosophila Embryo ◽

Upstream Region ◽

Enhancer Element ◽

Gap Gene ◽

Gap Genes ◽

Two Phases ◽

Necessary And Sufficient

The gap gene hunchback (hb) is required for the formation and segmentation of two regions of the Drosophila embryo, a broad anterior domain and a narrow posterior domain. Accumulation of hb transcript in the posterior of the embryo occurs in two phases, an initial cap covering the terminal 15% of the embryo followed by a stripe at the anterior edge of this region. By in situ hybridization with transcript-specific probes, we show that the cap is composed only of mRNA from the distal transcription initiation site (P1), while the later posterior stripe is composed of mRNA from both the distal and proximal (P2) transcription initiation sites. Using a series of genomic rescue constructs and promoter-lacZ fusion genes, we define a 1.4 kb fragment of the hb upstream region that is both necessary and sufficient for posterior expression. Sequences within this fragment mediate regulation by the terminal gap genes tailless (tll) and a huckebein, which direct the formation of the posterior hb stripe. We show that the tll protein binds in vitro to specific sites within the 1.4 kb posterior enhancer region, providing the first direct evidence for activation of gene expression by tll. We propose a model in which the anterior border of the posterior hb stripe is determined by tll concentration in a manner analogous to the activation of anterior hb expression by bicoid.

Download Full-text