The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNA

Little, Shawn C.; Tkačik, Gašper; Kneeland, Thomas B.; Wieschaus, Eric; Gregor, Thomas

doi:10.1371/journal.pbio.1000596

Cited by 165 publications

(270 citation statements)

References 56 publications

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“…There, each mRNA harbors a binding site of size c ~ 1-10 nm, but the mRNAs typically are separated by distances d ~ 1-10 μm. Roughly, we can expect that input readouts will be independent and the ITR mechanism effective so long as M ≲ d/ c ~ 10 2 -10 4 , putting M in the range that we examined and where it appears biologically plausible; recent experiments in the Drosophila and zebrafish embryos and in mammalian cells reported mRNA counts in the range 50-1200 per typical cell volume [79,[87][88][89][90][91]. For such values of M, we find significant increases in capacity of 0.8-1.8 bits at C ~ 0.1-1, with optimal regulatory curves using high…”

Section: Discussionmentioning

confidence: 99%

Extending the dynamic range of transcription factor action by translational regulation

Sokolowski¹,

Walczak²,

Bialek³

et al. 2016

Phys. Rev. E

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A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these molecules at their binding sites can severely limit the precision of regulation. Recent work on the optimization of information flow through regulatory networks indicates that the lower end of the dynamic range of concentrations is simply inaccessible, overwhelmed by the impact of this noise. Motivated by the behavior of homeodomain proteins, such as the maternal morphogen Bicoid in the fruit fly embryo, we suggest a scheme in which transcription factors also act as indirect translational regulators, binding to the mRNA of other regulatory proteins. Intuitively, each mRNA molecule acts as an independent sensor of the input concentration, and averaging over these multiple sensors reduces the noise. We analyze information flow through this scheme and identify conditions under which it outperforms direct transcriptional regulation. Our results suggest that the dual role of homeodomain proteins is not just a historical accident, but a solution to a crucial physics problem in the regulation of gene expression.

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Section: Discussionmentioning

confidence: 99%

Extending the dynamic range of transcription factor action by translational regulation

Sokolowski¹,

Walczak²,

Bialek³

et al. 2016

Phys. Rev. E

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“…1,2,4 A large number of experimental and theoretical investigations on the formation and functioning of morphogen gradients has appeared in recent years. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]21,22 However, many aspects of biological signaling remain not well understood. 4,6 One of the most important problems of the biological development is to understand the mechanisms of the morphogen gradients formation.…”

Section: Figure 0: Toc Graphicmentioning

confidence: 99%

New Model for Understanding Mechanisms of Biological Signaling: Direct Transport via Cytonemes

Teimouri

Kolomeisky

2015

J. Phys. Chem. Lett.

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Biological signaling is a crucial natural process that governs the formation of all multicellular organisms. It relies on efficient and fast transfer of information between different cells and tissues. It has been presumed for a long time that these long-distance communications in most systems can take place only indirectly via the diffusion of signaling molecules, also known as morphogens, through the extracellular fluid. However, recent experiments indicate that there is also an alternative direct delivery mechanism. It utilizes dynamic tubular cellular extensions, called cytonemes, that directly connect cells, supporting the flux of morphogens to specific locations. We present a first quantitative analysis of the cytoneme-mediated mechanism of biological signaling. Dynamics of the formation of signaling molecule profiles, which are also known as morphogen gradients, is discussed. It is found that the direct-delivery mechanism is more robust with respect to fluctuations in comparison with the passive diffusion mechanism. In addition, we show that the direct transport of morphogens through cytonemes

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“…Since the measured bcd mRNA profile differs from the exponential Bcd protein profile, 14 the pure form of the proposed mRNA-dictatedgradient model also appears inadequate for explaining fully how the Bcd protein gradient is formed. 12,16 In addition to these two contrasting models, several other models have also been proposed for Bcd. [17][18][19] Since Bcd diffusion remains a component of all these models, they as a group are more related to the diffusion model than the mRNA-dictated-gradient model.…”

Section: Morphogen Gradient Formation and Actionmentioning

confidence: 99%

Morphogen gradient formation and action

Liu

2011

Fly

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The Formation of the Bicoid Morphogen Gradient Requires Protein Movement from Anteriorly Localized mRNA

Abstract: New quantitative data show that the Bicoid morphogen gradient is generated from a dynamic localized source and that protein gradient formation requires protein movement along the anterior-posterior axis.

Cited by 165 publications

References 56 publications

Extending the dynamic range of transcription factor action by translational regulation

Extending the dynamic range of transcription factor action by translational regulation

New Model for Understanding Mechanisms of Biological Signaling: Direct Transport via Cytonemes

Morphogen gradient formation and action

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