The gap gene network

Jaeger, Johannes

doi:10.1007/s00018-010-0536-y

Cited by 287 publications

(393 citation statements)

References 360 publications

(690 reference statements)

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“…(B) A stripe-forming circuit uses one of six distinct mechanisms (6), each mechanism uses a distinct gene expression dynamics in space and time to reach the same phenotype. Importantly, Mutual Inhibition (bicoid-hunchback-knirps), Incoherent feed-forward (caudal-knirps-giant), and Classical (hunchback-krüppel-knirps) are involved in Drosophila anterior-posterior patterning (26), whereas Incoherent feed-forward controls the mesoderm inducer Xenopus Brachyury (27).…”

Section: Resultsmentioning

confidence: 99%

Dynamics of gene circuits shapes evolvability

Jiménez

Cotterell

Munteanu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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To what extent does the dynamical mechanism producing a specific biological phenotype bias the ability to evolve into novel phenotypes? We use the interpretation of a morphogen gradient into a single stripe of gene expression as a model phenotype. Although there are thousands of three-gene circuit topologies that can robustly develop a stripe of gene expression, the vast majority of these circuits use one of just six fundamentally different dynamical mechanisms. Here we explore the potential for gene circuits that use each of these six mechanisms to evolve novel phenotypes such as multiple stripes, inverted stripes, and gradients of gene expression. Through a comprehensive and systematic analysis, we find that circuits that use alternative mechanisms differ in the likelihood of reaching novel phenotypes through mutation. We characterize the phenotypic transitions and identify key ingredients of the evolutionary potential, such as sensitive interactions and phenotypic hubs. Finally, we provide an intuitive understanding on how the modular design of a particular mechanism favors the access to novel phenotypes. Our work illustrates how the dynamical mechanism by which an organism develops constrains how it can evolve. It is striking that these dynamical mechanisms and their impact on evolvability can be observed even for such an apparently simple patterning task, performed by just three-node circuits.

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Section: Resultsmentioning

confidence: 99%

Dynamics of gene circuits shapes evolvability

Jiménez

Cotterell

Munteanu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…According to this view, the mediolateral compartmentalization of the vertebrate ectoderm would operate in a manner similar to the Drosophila gap gene GRN (Jaeger, 2011): morphogens polarize and divide the ectoderm into broad territories, activating genes that will engage in multiple cross-regulatory interactions, resulting in the progressive restriction and delimitation of territories of cells sharing similar regulatory states.…”

Section: Induction and Formation Of The Neural Plate Bordermentioning

confidence: 99%

Establishing neural crest identity: a gene regulatory recipe

2015

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The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population.

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“…One advantage of querying functional dosage compensation with a segmentation gene is that it is relatively easy to trace any observed difference both upstream and downstream in the well-established regulatory network (Schroeder et al 2004;Jaeger 2011). It is known that the second stripe of eve, for example, is activated by Bicoid (Bcd) and Hunchback (Hb) and repressed in the anterior by Giant (Gt) and in the posterior by Krüppel (Kr) Stanojevic et al 1991;Small et al 1992).…”

mentioning

confidence: 99%

Sex-Specific Pattern Formation During Early Drosophila Development

2013

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The deleterious effects of different X-chromosome dosage in males and females are buffered by a process called dosage compensation, which in Drosophila is achieved through a doubling of X-linked transcription in males. The male-specific lethal complex mediates this process, but is known to act only after gastrulation. Recent work has shown that the transcription of X-linked genes is also upregulated in males prior to gastrulation; whether it results in functional dosage compensation is not known. Absent or partial early dosage compensation raises the possibility of sex-biased expression of key developmental genes, such as the segmentation genes controlling anteroposterior patterning. We assess the functional output of early dosage compensation by measuring the expression of even-skipped (eve) with high spatiotemporal resolution in male and female embryos. We show that eve has a sexually dimorphic pattern, suggesting an interaction with either X-chromosome dose or the sex determination system. By manipulating the gene copy number of an X-linked transcription factor, giant (gt), we traced sex-biased eve patterning to gt dose, indicating that early dosage compensation is functionally incomplete. Despite sex-biased eve expression, the gene networks downstream of eve are able to produce sex-independent segmentation, a point that we establish by measuring the proportions of segments in elongated germ-band embryos. Finally, we use a whole-locus eve transgene with modified cis regulation to demonstrate that segment proportions have a sexdependent sensitivity to subtle changes in Eve expression. The sex independence of downstream segmentation despite this sensitivity to Eve expression implies that additional autosomal gene-or pathway-specific mechanisms are required to ameliorate the effects of partial early dosage compensation. IN Drosophila, dosage compensation occurs by an upregulation of transcription from the X chromosome in males (Mukherjee and Beermann 1965;Belote and Lucchesi 1980;Straub et al. 2005). The best-characterized mechanism of upregulation depends on the male-specific activity of the malespecific lethal (MSL) complex (Gelbart and Kuroda 2009), which binds to sites on the X chromosome and enhances the rate of transcript elongation (Larschan et al. 2011). MSL activity is inhibited in females by the translational repression of Msl2 protein, which is necessary for complex formation, by the protein product of the sex-determination gene Sex-lethal (Sxl) (Kelley et al. 1995). The canonical MSL-dependent mechanism does not appear to be active prior to gastrulation as msl2 transcript is not detected until cleavage cycle 14 (Lott et al. 2011) and the earliest expression of Msl3 protein in male embryos is detected only at stage 6 (gastrulation) (Rastelli et al. 1995;Franke et al. 1996;Cline 2005).Despite the lack of MSL-dependent dosage compensation during the blastoderm stage, the transcription of X-linked genes expressed before gastrulation is, in fact, elevated in males (Lott et al. 2011). With the exc...

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The gap gene network

Cited by 287 publications

References 360 publications

Dynamics of gene circuits shapes evolvability

Dynamics of gene circuits shapes evolvability

Establishing neural crest identity: a gene regulatory recipe

Sex-Specific Pattern Formation During Early Drosophila Development

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