Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution, yet how they form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the early Drosophila embryo.听
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First, we use fluorescence correlation spectroscopy to examine protein dynamics听in vivo. We find there are spatial differences in听Bcd听diffusivity along the AP axis, with听Bcd听diffusing more rapidly in the posterior. We establish that such spatially varying differences in听Bcd dynamics are sufficient to explain how听Bcd听can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of听Bcd听near the posterior pole. In the nucleus, we demonstrate that听Bcd听dynamics are impacted by binding to DNA. Addition of the听Bcd听homeodomain to听eGFP::NLS qualitatively replicates the听Bcd concentration profile, suggesting this domain regulates听Bcd听dynamics. Our results reveal how a long-range gradient can form while retaining a steep profile through much of its range.
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Second,听we take advantage of the听SunTag听reporter system to quantitatively examine the spatiotemporal profile of听bcd听mRNA translation听in vivo. We demonstrate that Processing body (P body) localisation in the oocyte suppresses premature听bcd听mRNA translation. Upon egg laying,听bcd听mRNA disassociates from P bodies and translation is observed exclusively in the anterior pole of the embryo. Accompanying nuclear migration to the embryo cortex at nuclear cycle (n.c.) 9,听bcd听mRNA relocates to the apical domain of the nuclear environment and translation continues near the embryo surface. In听n.c.听14,听bcd听mRNA localises to newly formed P bodies and further translation is not detected.听
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We use these observations to build a modified source-diffusion-degradation model of听Bcd gradient formation that leads to an exponential gradient by听n.c.听12 and is consistent with other experimental measurements of听Bcd听dynamics. Consequently, we see that the spatiotemporal dynamics of Bicoid听are highly regulated throughout oogenesis and early embryo development.