Dynamics of the Dorsal morphogen gradient

Abstract

The dorsoventral (DV) patterning of the Drosophila embryo depends on the nuclear localization gradient of Dorsal (Dl), a protein related to the mammalian NF-B transcription factors. Current understanding of how the Dl gradient works has been derived from studies of its transcriptional interpretation, but the gradient itself has not been quantified. In particular, it is not known whether the Dl gradient is stable or dynamic during the DV patterning of the embryo. To address this question, we developed a mathematical model of the Dl gradient and constrained its parameters by experimental data. Based on our computational analysis, we predict that the Dl gradient is dynamic and, to a first approximation, can be described as a concentration profile with increasing amplitude and constant shape. These timedependent properties of the Dl gradient are different from those of the Bicoid and MAPK phosphorylation gradients, which pattern the anterior and terminal regions of the embryo. Specifically, the gradient of the nuclear levels of Bicoid is stable, whereas the pattern of MAPK phosphorylation changes in both shape and amplitude. We attribute these striking differences in the dynamics of maternal morphogen gradients to the differences in the initial conditions and chemistries of the anterior, DV, and terminal systems.computational modeling ͉ Drosophila ͉ systems biology ͉ parameter estimation A tissue patterned by morphogen gradients can change its transcriptional state, grow, or deform either in response to the gradients or independently of them (1-3). When these changes are much slower than the dynamics of the gradient, a tissue responds to a stable signal. Transcriptional interpretation of such signals can rely on differences in the expression thresholds of target genes with respect to the spatially distributed repressors or activators (2, 4). A different strategy for signal interpretation is required when the formation of positional information becomes intertwined with the dynamics of the patterned system (2, 5). Here, we suggest that the dorsoventral (DV) patterning of the Drosophila embryo operates in this regime.The DV patterning of the Drosophila embryo depends on the nuclear localization gradient of Dorsal (Dl), a protein related to the NF-B family of transcription factors (6-10). Transcriptional interpretation of the Dl gradient depends on the differences in the affinities of the Dl binding sites in the Dl-target genes and several gene expression and signaling cascades initiated by Dl (6,11,12). A ventral-to-dorsal occupancy gradient of the Toll cell surface receptor provides the activating signal for the DV patterning (13). In the absence of this signal, Dl is sequestered in the cytoplasm, in complex with an inhibitory protein I-B, called Cactus (Cact) in Drosophila. In response to Toll signaling, the Dl-Cact complex dissociates, Cact is degraded, and Dl enters the nucleus to control gene expression. In the current model of DV patterning, positional information is established by the spatial pattern of Toll occ...

Capicua DNA-binding sites are general response elements for RTK signaling inDrosophila

“…During DV patterning, the Dorsal morphogen activates the expression of several targets in ventral and lateral regions of the embryo, and it is believed that decreasing amounts of Dorsal protein help establish the dorsal limits of those expression domains. However, Dorsal nuclear levels appear rather uniform across the ind expression domain (Kanodia et al, 2009;Liberman et al, 2009), indicating that other mechanisms define the dorsal limit of ind expression. Indeed, previous studies have shown that EGFR signaling plays a key role in setting this border (Weiss et al, 1998;von Ohlen and Doe, 2000), and suggested the existence of unknown repressors restricting ind expression in dorsal regions (Stathopoulos and Levine, 2005).…”

The evolution of dorsal–ventral patterning mechanisms in insects

“…Toll activation occurs in a gradient emanating from the ventral midline, leading to a corresponding gradient of Dorsal nuclear uptake. This gradient is stable throughout the 14th synchronous nuclear division cycle, when most embryonic patterning takes place, and shows a similar shape with lower amplitude during the preceding five syncytial divisions (Kanodia et al 2009;). The graded pattern of nuclear Dorsal uptake is not simply a readout of the ventral pipe expression pattern in the ovarian follicle cells, because the latter is expressed uniformly in its domain ( Fig.…”

Actomyosin-based tissue folding requires a multicellular myosin gradient

“…It has been previously shown that Dorsal, a maternal morphogen that is required for twist transcription, is active in a gradient along the ventral-lateral axis with highest nuclear levels in the most ventral cells (Kanodia et al, 2009;Reeves et al, 2012). twist expression levels have previously been described as being uniform across the central region of the ventral furrow with a gradient of twist at the edge of the furrow, where cells stretch (Leptin, 1991).…”