A WntD-Dependent Integral Feedback Loop Attenuates Variability in Drosophila Toll Signaling

Rahimi, Neta; Averbukh, Inna; Haskel‐Ittah, Michal; Degani, Neta; Schejter, Eyal D.; Barkai, Naama; Shilo, Ben‐Zion

doi:10.1016/j.devcel.2016.01.023

Cited by 39 publications

(46 citation statements)

References 41 publications

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“…The wntD gene functions as a feedback inhibitor of the Toll/Dorsal pathway, with ectopic wntD expression blocking Dorsal activation (Ganguly et al 2005;Gordon et al 2005). The presence of feedback inhibition in this genetic network appears to promote robustness in the positional expression of genes downstream of Dorsal (Rahimi et al 2016(Rahimi et al , 2019.…”

Section: Gene Expression: Snailmentioning

confidence: 99%

The Physical Mechanisms ofDrosophilaGastrulation: Mesoderm and Endoderm Invagination

Martin

2020

Genetics

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A critical juncture in early development is the partitioning of cells that will adopt different fates into three germ layers: the ectoderm, the mesoderm, and the endoderm. This step is achieved through the internalization of specified cells from the outermost surface layer, through a process called gastrulation. In Drosophila, gastrulation is achieved through cell shape changes (i.e., apical constriction) that change tissue curvature and lead to the folding of a surface epithelium. Folding of embryonic tissue results in mesoderm and endoderm invagination, not as individual cells, but as collective tissue units. The tractability of Drosophila as a model system is best exemplified by how much we know about Drosophila gastrulation, from the signals that pattern the embryo to the molecular components that generate force, and how these components are organized to promote cell and tissue shape changes. For mesoderm invagination, graded signaling by the morphogen, Spätzle, sets up a gradient in transcriptional activity that leads to the expression of a secreted ligand (Folded gastrulation) and a transmembrane protein (T48). Together with the GPCR Mist, which is expressed in the mesoderm, and the GPCR Smog, which is expressed uniformly, these signals activate heterotrimeric G-protein and small Rho-family G-protein signaling to promote apical contractility and changes in cell and tissue shape. A notable feature of this signaling pathway is its intricate organization in both space and time. At the cellular level, signaling components and the cytoskeleton exhibit striking polarity, not only along the apical–basal cell axis, but also within the apical domain. Furthermore, gene expression controls a highly choreographed chain of events, the dynamics of which are critical for primordium invagination; it does not simply throw the cytoskeletal “on” switch. Finally, studies of Drosophila gastrulation have provided insight into how global tissue mechanics and movements are intertwined as multiple tissues simultaneously change shape. Overall, these studies have contributed to the view that cells respond to forces that propagate over great distances, demonstrating that cellular decisions, and, ultimately, tissue shape changes, proceed by integrating cues across an entire embryo.

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Section: Gene Expression: Snailmentioning

confidence: 99%

The Physical Mechanisms ofDrosophilaGastrulation: Mesoderm and Endoderm Invagination

Martin

2020

Genetics

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“…One mechanism that could explain this phenotype is saturation of active Toll receptors. If the domain of active Toll signaling is graded in space (Haskel-Ittah et al, 2012;Rahimi et al, 2016), active Toll receptors should be limiting at the domain edge. If active Toll saturation is sufficiently extensive in wild-type embryos, then the formation of a smooth peak is the result of sufficient numbers of Dl/Cact complexes bypassing the saturated Toll regime and arriving at the ventral midline ( Fig.…”

Section: Decreased Diffusion Of the Dl/cact Complex Widens The DL Gramentioning

confidence: 99%

A facilitated diffusion mechanism establishes the Drosophila Dorsal gradient

et al. 2017

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The transcription factor NF-κB plays an important role in the immune system, apoptosis and inflammation. Dorsal, a homolog of NF-κB, patterns the dorsal-ventral axis in the blastoderm embryo. During this stage, Dorsal is sequestered outside the nucleus by the IκB homolog Cactus. Toll signaling on the ventral side breaks the Dorsal/Cactus complex, allowing Dorsal to enter the nucleus to regulate target genes. Fluorescent data show that Dorsal accumulates on the ventral side of the syncytial blastoderm. Here, we use modeling and experimental studies to show that this accumulation is caused by facilitated diffusion, or shuttling, of the Dorsal/Cactus complex. We also show that active Toll receptors are limiting in wild-type embryos, which is a key factor in explaining global Dorsal gradient formation. Our results suggest that shuttling is necessary for viability of embryos from mothers with compromised levels. Therefore, Cactus not only has the primary role of regulating Dorsal nuclear import, but also has a secondary role in shuttling. Given that this mechanism has been found in other, independent, systems, we suggest that it might be more prevalent than previously thought.

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“…A classic paradigm for this one-to-many mapping is the idea of a morphogen, a substance whose concentration varies with embryonic position and where different concentrations are sufficient to induce different cell fates (Gurdon et al, 1998). Alternatively, cell fates may be specified by combinatorial control: the spatial overlap between particular combinations of patterning cues (Rahimi et al, 2016). A third model, dynamic control, holds that a single signal could select among cellular responses based on features such as the amplitude, duration, or frequency of pathway activation (Imayoshi et al, 2013;Purvis and Lahav, 2013).…”

Section: Introductionmentioning

confidence: 99%