PT  - JOURNAL ARTICLE
AU  - Neta Rahimi
AU  - Inna Averbukh
AU  - Shari Carmon
AU  - Eyal D. Schejter
AU  - Naama Barkai
AU  - Ben-Zion Shilo
TI  - Dynamics of Spaetzle morphogen shuttling in the <em>Drosophila</em> embryo shapes pattern
AID  - 10.1101/505925
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 505925
4099  - http://biorxiv.org/content/early/2018/12/27/505925.short
4100  - http://biorxiv.org/content/early/2018/12/27/505925.full
AB  - Establishment of morphogen gradients in the early Drosophila embryo is challenged by a diffusible extracellular milieu, and rapid nuclear divisions that occur at the same time. To understand how a sharp gradient is formed within this dynamic environment, we followed the generation of graded nuclear Dorsal (Dl) protein, the hallmark of pattern formation along the dorso-ventral axis, in live embryos. We show that a sharp gradient is formed through extracellular, diffusion-based morphogen shuttling that progresses through several nuclear divisions. Perturbed shuttling in wntD mutant embryos results in a flat activation peak and aberrant gastrulation. Re-entry of Dl into the nuclei at each cycle refines the signaling output, by guiding graded accumulation of the T48 transcript that drives patterned gastrulation. We conclude that diffusion-based ligand shuttling, coupled with dynamic readout, establishes a refined pattern within the diffusible environment of early embryos.