Combined Sequenced-Based Model of the Drosophila Gap Gene Network

AbstractGap 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.

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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.

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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.

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

eLife ◽

10.7554/elife.41208 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 3

Author(s):

Alena Boos ◽

Jutta Distler ◽

Heike Rudolf ◽

Martin Klingler ◽

Ezzat El-Sherif

Keyword(s):

Gene Network ◽

Hox Genes ◽

Morphogen Gradient ◽

Regulation Mechanism ◽

Morphogen Gradients ◽

Gap Gene ◽

Speed Regulation ◽

Gap Genes ◽

Anterior Posterior ◽

Anterior Posterior Axis

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.

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The gap gene network

Cellular and Molecular Life Sciences ◽

10.1007/s00018-010-0536-y ◽

2010 ◽

Vol 68 (2) ◽

pp. 243-274 ◽

Cited By ~ 172

Author(s):

Johannes Jaeger

Keyword(s):

Gene Network ◽

Gap Gene

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Bayesian model selection for the Drosophila gap gene network

BMC Bioinformatics ◽

10.1186/s12859-019-2888-0 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Asif Zubair ◽

I. Gary Rosen ◽

Sergey V. Nuzhdin ◽

Paul Marjoram

Keyword(s):

Model Selection ◽

Bayesian Model ◽

Gene Network ◽

Bayesian Model Selection ◽

Gap Gene ◽

Selection For

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Morphogenesis at criticality

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1324186111 ◽

2014 ◽

Vol 111 (10) ◽

pp. 3683-3688 ◽

Cited By ~ 63

Author(s):

Dmitry Krotov ◽

Julien O. Dubuis ◽

Thomas Gregor ◽

William Bialek

Keyword(s):

Transcription Factors ◽

Spatial Patterns ◽

Gaussian Distribution ◽

Gene Network ◽

Fruit Fly ◽

Genetic Network ◽

Strong Correlations ◽

Expression Levels ◽

Gap Gene ◽

Gap Genes

Spatial patterns in the early fruit fly embryo emerge from a network of interactions among transcription factors, the gap genes, driven by maternal inputs. Such networks can exhibit many qualitatively different behaviors, separated by critical surfaces. At criticality, we should observe strong correlations in the fluctuations of different genes around their mean expression levels, a slowing of the dynamics along some but not all directions in the space of possible expression levels, correlations of expression fluctuations over long distances in the embryo, and departures from a Gaussian distribution of these fluctuations. Analysis of recent experiments on the gap gene network shows that all these signatures are observed, and that the different signatures are related in ways predicted by theory. Although there might be other explanations for these individual phenomena, the confluence of evidence suggests that this genetic network is tuned to criticality.

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Trading bits in the readout from a genetic network

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2109011118 ◽

2021 ◽

Vol 118 (46) ◽

pp. e2109011118

Author(s):

Marianne Bauer ◽

Mariela D. Petkova ◽

Thomas Gregor ◽

Eric F. Wieschaus ◽

William Bialek

Keyword(s):

Gene Network ◽

Regulation Of Gene Expression ◽

Relevant Information ◽

Genetic Network ◽

Fine Tuning ◽

Theoretic Approach ◽

Information Theoretic ◽

Gap Gene ◽

Optimal Information ◽

Information Theoretic Approach

In the regulation of gene expression, information of relevance to the organism is represented by the concentrations of transcription factor molecules. To extract this information the cell must effectively “measure” these concentrations, but there are physical limits to the precision of these measurements. We use the gap gene network in the early fly embryo as an example of the tradeoff between the precision of concentration measurements and the transmission of relevant information. For thresholded measurements we find that lower thresholds are more important, and fine tuning is not required for near-optimal information transmission. We then consider general sensors, constrained only by a limit on their information capacity, and find that thresholded sensors can approach true information theoretic optima. The information theoretic approach allows us to identify the optimal sensor for the entire gap gene network and to argue that the physical limitations of sensing necessitate the observed multiplicity of enhancer elements, with sensitivities to combinations rather than single transcription factors.

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Author response: Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita

10.7554/elife.04785.023 ◽

2014 ◽

Author(s):

Karl R Wotton ◽

Eva Jiménez-Guri ◽

Anton Crombach ◽

Hilde Janssens ◽

Anna Alcaine-Colet ◽

...

Keyword(s):

Gene Network ◽

Author Response ◽

Gap Gene ◽

Megaselia Abdita

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