Bicoid cooperative DNA binding is critical for embryonic patterning in
            <i>Drosophila</i>

Lebrecht, Danielle; Foehr, Marisa L.; Smith, Eric M.; Lopes, Francisco J. P.; Vanario-Alonso, Carlos E.; Reinitz, John; Burz, David S.; Hanes, Steven D.

doi:10.1073/pnas.0506462102

Cited by 111 publications

(106 citation statements)

References 51 publications

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“…Also, cooperative binding of Bcd to target genes has been shown. 9,10 In this case, the binding of Bcd to a high affinity site would promote the binding of Bcd to a low affinity site in the vicinity.…”

Section: Bicoidmentioning

confidence: 99%

Bicoid - morphogen function revisited

Löhr

Chung

Beller

et al. 2010

Fly

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Section: Bicoidmentioning

confidence: 99%

Bicoid - morphogen function revisited

Löhr

Chung

Beller

et al. 2010

Fly

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Section: Combinatorial Inputsmentioning

confidence: 99%

“…Therefore, Bcd binding to a high-affinity site potentiates binding to an adjacent low-affinity site (Burz et al, 1998). Expression of a Bcd protein with a mutation that disrupts cooperativity in the embryo leads to an anterior shift in the expression patterns of target genes, such as hb, and reduced sharpness of their posterior borders (Lebrecht et al, 2005).The integration of inputs from Dl and from other transcription factors also influences the response of genes along the DV axis of the Drosophila embryo. An analysis of Dl target gene enhancers in different Drosophilids (Papatsenko and Levine, 2005) has revealed that, just as type I threshold genes tend to have lower Dl affinity than do type II genes, there is a similar trend in these promoters for the affinity of another transcription factor, Twi.…”

mentioning

confidence: 99%

The interpretation of morphogen gradients

Ashe

Briscoe²

2006

Development

452

381

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DEVELOPMENT 385Morphogens act as graded positional cues that control cell fate specification in many developing tissues. This concept, in which a signalling gradient regulates differential gene expression in a concentration-dependent manner, provides a basis for understanding many patterning processes. It also raises several mechanistic issues, such as how responding cells perceive and interpret the concentration-dependent information provided by a morphogen to generate precise patterns of gene expression and cell differentiation in developing tissues. Here, we review recent work on the molecular features of morphogen signalling that facilitate the interpretation of graded signals and attempt to identify some emerging common principles. IntroductionThe transformation of the spatial distribution of naïve cells in a developing tissue into an organised arrangement of cell differentiation is fundamental to the development of multicellular organisms. More than a century ago, evidence began to accumulate that cells receive 'positional information' that instructs them to develop in specific ways, depending on their location within a tissue (Wolpert, 1996). Over the intervening decades, the potential for signalling gradients to provide this positional information has become a much-investigated and -debated subject, and the term 'morphogen' has been coined to describe such signals. Today the morphogen concept continues to form the basis of many models of pattern formation (Lewis et al., 1977;Green and Smith, 1991;Gurdon and Bourillot, 2001;Tabata and Takei, 2004). Typically, in current models it is proposed that a signal produced from a defined localised source forms a concentration gradient as it spreads through surrounding tissue (Fig. 1A). The graded signal then acts directly on cells, in a concentration-dependent manner, to specify gene expression changes and cell fate selection. Thus, the concentration of ligand provides cells with a measure of their position relative to the source of the signal and organises the pattern of cell differentiation. Experimental evidence from tissues in both vertebrates and invertebrates indicates that several molecules appear to function as graded signals. The roles of these signals range from the establishment of the initial polarities of embryos to specification of cell identity in specific tissues, notably limb appendages and the nervous system in both vertebrates and Drosophila. The examples we focus on in this review are introduced in Fig. 1. Evidence in support of these signals acting as graded morphogens has been summarised in recent reviews (Gurdon and Bourillot, 2001;Tabata and Takei, 2004).Although the morphogen concept has provided an enduring and valid framework for understanding pattern formation, it raises many mechanistic issues. Much attention has focused on how the distribution of a morphogen through a tissue establishes and maintains a gradient of activity (Vincent and Dubois, 2002;Tabata and Takei, 2004); however, how the signal is perceived and interpreted in a grad...

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“…This gradient determines the boundary of expression of downstream effectors such as Hunchback, eventually leading to the establishment of the segmented body plan. The dynamics of Bicoid pattern formation were recently studied in several experiments (8)(9)(10)(11)(12)(13)(14)(15). The gradient was found to have, to a good approximation, an exponential decay with distance from the anterior.…”

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confidence: 99%

Determining the scale of the Bicoid morphogen gradient

Hecht

Rappel

Levine

2009

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

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Bicoid is a morphogen that sets up the anterior-posterior axis in early Drosophila embryos. Although the form of the Bicoid profile is consistent with a simple diffusion/degradation model, the observed length scale is much larger than should be expected based on the measured diffusion rate. Here, we study two possible mechanisms that could, in principle, affect this gradient and, hence, address this disagreement. First, we show that including trapping and release of Bicoid by the nuclei during cleavage cycles does not alter the morphogen length scale. More crucially, the inclusion of advective transport due to cytoplasmic streaming can have a large effect. Specifically, we build a simple model based on the (limited) experimental data and show that such a flow can lead to a Bicoid profile that is consistent with various experimental features. Specifically, the observed length scale is obtained, a steady profile is established, and improved scaling between embryos of different lengths is demonstrated.Drosophila ͉ embryonic development ͉ flow ͉ length scale D uring embryonic development, originally identical cells need to appropriately differentiate into a large variety of cell fates. This differentiation is position-dependent and is regulated by diffusible signaling molecules, known as morphogens. Morphogens are produced in a specific region of a tissue and move away from their source to form long-range concentration gradients. Cells subsequently differentiate in response to the morphogen concentration (1-2); thus, the pattern of morphogen concentration is crucial to the functional formation of tissues and organisms.In Drosophila melanogaster, Bicoid is a maternally transcribed gene that organizes anterior development (3-6). Its mRNA is localized at the anterior pole of the oocyte and is translated shortly after egg deposition. As a consequence of the anterior localization of mRNA, a gradient of Bicoid is formed along the anterior-posterior (AP) axis, simultaneously with nuclear cleavage cycles (7). This gradient determines the boundary of expression of downstream effectors such as Hunchback, eventually leading to the establishment of the segmented body plan. The dynamics of Bicoid pattern formation were recently studied in several experiments (8-15). The gradient was found to have, to a good approximation, an exponential decay with distance from the anterior. The exponential profile is consistent with the general model of diffusion and constant degradation rate which gives a length scale of ͌ D/␦, where D is the diffusion constant and ␦ is the degradation constant.This simple diffusion/degradation picture, however, turns out to be inconsistent with several recent experiments. In one such experiment (13), the Bicoid diffusion constant was measured using fluorescence measurements of Bicoid-eGFP protein in the nuclei. Upon photobleaching, the recovery rate of nuclear Bicoid was determined, and a diffusion constant of D ϭ 0.27 m 2 /s was obtained. With no degradation, this would lead to a length scale of ϭ ͌ DT where...

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Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila

Cited by 111 publications

References 51 publications

Bicoid - morphogen function revisited

Bicoid - morphogen function revisited

The interpretation of morphogen gradients

Determining the scale of the Bicoid morphogen gradient

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