TY - JOUR
T1 - Dynamics of the Dorsal morphogen gradient
AU - Kanodia, Jitendra S.
AU - Rikhy, Richa
AU - Kim, Yoosik
AU - Lund, Viktor K.
AU - DeLotto, Robert
AU - Lippincott-Schwartz, Jennifer
AU - Shvartsman, Stanislav Y.
PY - 2009/12/22
Y1 - 2009/12/22
N2 - The dorsoventral (DV) patterning of the Drosophila embryo depends on the nuclear localization gradient of Dorsal (Dl), a protein related to the mammalian NF-κB 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 theDVpatterning 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 time-dependent 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.
AB - The dorsoventral (DV) patterning of the Drosophila embryo depends on the nuclear localization gradient of Dorsal (Dl), a protein related to the mammalian NF-κB 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 theDVpatterning 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 time-dependent 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.
KW - Computational modeling
KW - Drosophila
KW - Parameter estimation
KW - Systems biology
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U2 - 10.1073/pnas.0912395106
DO - 10.1073/pnas.0912395106
M3 - Article
C2 - 19996178
AN - SCOPUS:76049127722
SN - 0027-8424
VL - 106
SP - 21707
EP - 21712
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 51
ER -