10 research outputs found
Feedback control of the EGFR signaling gradient: superposition of domain-splitting events in Drosophila oogenesis
The morphogenesis of structures with repeated functional units, such as
body segments and appendages, depends on multi-domain patterns of cell
signaling and gene expression. We demonstrate that during Drosophila
oogenesis, the two-domain expression pattern of Broad, a transcription factor
essential for the formation of the two respiratory eggshell appendages, is
established by a single gradient of EGFR activation that induces both Broad
and Pointed, which mediates repression of Broad. Two negative-feedback loops
provided by the intracellular inhibitors of EGFR signaling, Kekkon-1 and
Sprouty, control the number and position of Broad-expressing cells and in this
way influence eggshell morphology. Later in oogenesis, the gradient of EGFR
activation is split into two smaller domains in a process that depends on
Argos, a secreted antagonist of EGFR signaling. In contrast to the previously
proposed model of eggshell patterning, we show that the two-domain pattern of
EGFR signaling is not essential for specifying the number of appendages. Thus,
the processes that define the two-domain patterns of Broad and EGFR activation
are distinct; their actions are separated in time and have different effects
on eggshell morphology
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A microfluidic array for large-scale ordering and orientation of embryos
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A computational statistics approach for estimating the spatial range of morphogen gradients
A crucial issue in studies of morphogen gradients relates to their range: the distance over which they can act as direct regulators
of cell signaling, gene expression and cell differentiation. To address this, we present a straightforward statistical framework that
can be used in multiple developmental systems. We illustrate the developed approach by providing a point estimate and
confidence interval for the spatial range of the graded distribution of nuclear Dorsal, a transcription factor that controls the
dorsoventral pattern of the Drosophila embryo
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Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Plamotamab Combined with Tafasitamab (Tafa) + Lenalidomide (Len) Vs Tafa+Len in Relapsed or Refractory DLBCL
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A microfluidic array for large-scale ordering and orientation of embryos
Quantitative studies of embryogenesis require the ability to monitor pattern formation and morphogenesis in large numbers of embryos, at multiple time points, and in diverse genetic backgrounds. We describe a simple approach that greatly facilitates these tasks for Drosophila melanogaster embryos, one of the most advanced models of developmental genetics. Based on passive hydrodynamics, we developed a microfluidic embryo trap array that rapidly orders and vertically orients hundreds of embryos. We describe the physical principles of the design and use this platform for the quantitative analysis of multiple morphogen gradients in the dorsoventral patterning system. Our approach can also be used for live imaging, and, with slight modifications, could be adapted for studies of pattern formation and morphogenesis in other model organisms