Known maternal gradients are not sufficient for the establishment of gap domains in Drosophila melanogaster

Jaeger, Johannes; Sharp, David H.; Reinitz, John

doi:10.1016/j.mod.2006.11.001

Cited by 76 publications

(137 citation statements)

References 90 publications

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“…In one view, information-rich maternal gradients provide all the spatial cues for the final patterns and the information is relayed in a step-by-step feed-forward manner, consistent with the traditional threshold-dependent readout model (6). In the other view, maternal gradients provide the initial spatial cues to downstream genes that then cross-regulate in an otherwise self-organized network (7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 59%

Dynamic interpretation of maternal inputs by the Drosophila segmentation gene network

Liu

Morrison

Gregor

2013

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

114

166

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Patterning of body parts in multicellular organisms relies on the interpretation of transcription factor (TF) concentrations by genetic networks. To determine the extent by which absolute TF concentration dictates gene expression and morphogenesis programs that ultimately lead to patterns in Drosophila embryos, we manipulate maternally supplied patterning determinants and measure readout concentration at the position of various developmental markers. When we increase the overall amount of the maternal TF Bicoid (Bcd) fivefold, Bcd concentrations in cells at positions of the cephalic furrow, an early morphological marker, differ by a factor of 2. This finding apparently contradicts the traditional thresholddependent readout model, which predicts that the Bcd concentrations at these positions should be identical. In contrast, Bcd concentration at target gene expression boundaries is nearly unchanged early in development but adjusts dynamically toward the same twofold change as development progresses. Thus, the Drosophila segmentation gene network responds faithfully to Bcd concentration during early development, in agreement with the threshold model, but subsequently partially adapts in response to altered Bcd dosage, driving segmentation patterns toward their WT positions. This dynamic response requires other maternal regulators, such as Torso and Nanos, suggesting that integration of maternal input information is not achieved through molecular interactions at the time of readout but through the subsequent collective interplay of the network.gap genes | gene regulatory networks | pattern formation T he macroscopic patterns of multicellular organisms are established by the molecular interplay within transcription factor (TF) networks that give rise to corresponding patterns of gene expression during the earliest stages of embryonic development (1). During these stages, individual cells acquire information about their position within the embryo by interpreting multiple TF concentration gradients and other factors that are inhomogeneously distributed in the egg (2-5). However, the quantitative and dynamic nature of this interpretation and the subsequent response of the network are not well understood. Specifically, little is known about the ability of individual DNA loci to measure TF concentrations precisely or how these loci integrate information from measurements of multiple input concentrations. One can distinguish between two broad classes of system-level viewpoints of how this information is interpreted by the network. In one view, information-rich maternal gradients provide all the spatial cues for the final patterns and the information is relayed in a step-by-step feed-forward manner, consistent with the traditional threshold-dependent readout model (6). In the other view, maternal gradients provide the initial spatial cues to downstream genes that then cross-regulate in an otherwise self-organized network (7-16).The Drosophila embryo provides an excellent system in which these problems can be addressed in a...

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confidence: 59%

Dynamic interpretation of maternal inputs by the Drosophila segmentation gene network

Liu

Morrison

Gregor

2013

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

114

166

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“…We argue that this will be the case if gap genes begin to be expressed prior to division cycle 14, as most experimental evidence indicates [23][24][25][26], due to the presteady state of the Bcd gradient and to increased inter-nuclear distance during these stages. At earlier cycles, the number of nuclei is small and they are more widely spread, leading to larger differences in Bcd concentration between neighboring nuclei.…”

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confidence: 87%

Improved readout precision of the Bicoid morphogen gradient by early decoding

Tamari

Barkai

2011

J Biol Phys

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Transcription factors (TFs) bind to specific DNA sequences to induce or repress gene expression. Expression levels can be tuned by changing TF concentrations, but the precision of such tuning is limited, since the fraction of time a TF occupies its binding site is subject to stochastic fluctuations. Bicoid (Bcd) is a TF that patterns the early Drosophila embryo by establishing an anterior-to-posterior concentration gradient and activating specific gene targets ("gap genes") in a concentration-dependent manner. Recently, the Bcd gradient and its in-vivo diffusion were quantified in live embryos, raising a quandary: the precision by which the Bcd target genes are defined (one-cell resolution) appeared to exceed the physical limits set by the stochastic binding of Bcd to DNA. We hypothesize that early readout of Bcd could account for the observed precision. Specifically, we consider the possibility that gap genes begin to be expressed earlier than typically measured experimentally, at a time when the distance between the nuclei is large. At this time, the difference in Bcd concentration between adjacent nuclei is large, enabling better tolerance for measurement imprecision. We show that such early decoding can indeed increase the accuracy of gap-gene expression, and that the initial pattern can be stabilized during subsequent divisions.

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“…The transcription of Bicoid target genes has been observed as early as cycle 10 ( Knipple et al, 1985;Tautz et al, 1987;Jaeger et al, 2007). At this stage, for certain Bicoid lifetime values, the gradient might be far from its steady state (Fig.…”

Section: When Is the Gradient Utilised?mentioning

confidence: 99%

Modelling the Bicoid gradient

2010

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SummaryMorphogen gradients provide embryonic tissues with positional information by inducing target genes at different concentration thresholds and thus at different positions. The Bicoid morphogen gradient in Drosophila melanogaster embryos has recently been analysed quantitatively, yet how it forms remains a matter of controversy. Several biophysical models that rely on production, diffusion and degradation have been formulated to account for the observed dynamics of the Bicoid gradient, but no one model can account for all its characteristics. Here, we discuss how existing data on this gradient fit the various proposed models and what aspects of gradient formation these models fail to explain. We suggest that knowing a few additional parameters, such as the lifetime of Bicoid, would help to identify and develop better models of Bicoid gradient formation.

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Known maternal gradients are not sufficient for the establishment of gap domains in Drosophila melanogaster

Cited by 76 publications

References 90 publications

Dynamic interpretation of maternal inputs by the Drosophila segmentation gene network

Dynamic interpretation of maternal inputs by the Drosophila segmentation gene network

Improved readout precision of the Bicoid morphogen gradient by early decoding

Modelling the Bicoid gradient

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