The Wg and Dpp morphogens regulate gene expression by modulating the frequency of transcriptional bursts

Abstract

<jats:p>Morphogen signaling contributes to the patterned spatiotemporal expression of genes during development. One mode of regulation of signaling-responsive genes is at the level of transcription. Single-cell quantitative studies of transcription have revealed that transcription occurs intermittently, in bursts. Although the effects of many gene regulatory mechanisms on transcriptional bursting have been studied, it remains unclear how morphogen gradients affect this dynamic property of downstream genes. Here we have adapted single molecule fluorescence in situ hybridization (smFISH) for use in the Drosophila wing imaginal disc in order to measure nascent and mature mRNA of genes downstream of the Wg and Dpp morphogen gradients. We compared our experimental results with predictions from stochastic models of transcription, which indicated that the transcription levels of these genes appear to share a common method of control via burst frequency modulation. Our data help further elucidate the link between developmental gene regulatory mechanisms and transcriptional bursting.</jats:p>

Single-Molecule FISH Reveals Subcellular Localization of α-Amylase and Actin mRNAs in the Filamentous Fungus Aspergillus oryzae

“…In multicellular cells for studying the regulation of gene expression, the fruit fly Drosophila is known to be a model organism, in which morphogens are key factors to organize gene expression ( Tabata and Takei, 2004 ; Bakker et al, 2020 ). However, little is known about how gene expression is regulated in other multicellular organisms, including filamentous fungi.…”

Cost-precision trade-off relation determines the optimal morphogen gradient for accurate biological pattern formation

“…We consider a morphogen production-independent quantity by taking the product of total cost and the squared relative error to quantify the trade-off between the cost and precision of the morphogen profile, and show that the trade-off product can be minimized when the morphogen gradient's characteristic length, λ, is properly selected. We evaluate the costeffectiveness of morphogen profiles patterning the fruit fly embryo and wing disk, which have been quantitatively characterized [4][5][6]10,33,[39][40][41][42][43][44] .…”

“…2H of Ref. 33 . Finally, the radius of the sensor for Dpp and Hh mediated patterning was set to a = 2 µm, same as for Wg, since they diffuse through the same wing imaginal disk.…”

“…It is of great interest to compare x b and λ of real morphogen profiles against the optimal λ min (x b ). For Bcd, Wg, Hh, and Dpp morphogen profiles, we first estimated the possible range of x b from the experimentally measured expression profiles of the respective target genes, hb, sens, dpp and salm 33,42,48 , and then found that the characteristic lengths of the four morphogen profiles, λ Bcd = 100 µm, λ Wg = 6 µm, λ Hh = 8 µm, and λ Dpp = 20 µm, are close to their respective optimal values, λ min (x b ) 4,5 . Thus, our findings indicate that the concentration profiles of the four morphogens are effectively formed at the lower bound of the costprecision trade-off, π o,min (x b ) (Fig.…”

“…Wg, a member of the Wnt signaling pathway, spreads through the wing disk from a narrow band of cells at the DV boundary 30,31 . The Wg concentration profile leads to the differential activation of multiple target genes, and, in particular, induces the sharp expression boundary of senseless (sens) a few cells away from the DV boundary 32,33 . Similarly, Hh patterns the AP axis by spreading from the posterior to the anterior side of the wing disk, affecting the expression of multiple genes.…”