Many conserved morphogenetic processes are orchestrated by a well-controlled interplay between mechanical forces and biochemical regulation. A key example is the early embryonic development of the Caenorhabditis elegans zygote, where large-scale flows of the actomyosin cortex occur simultaneously with the establishment of a polarity pattern in partitioning defective (PAR) proteins. However, how the PAR system interacts with and regulates cortical flow has remained elusive. By combining quantitative fluorescence microscopy, cell biology analysis and a physical theory, we here identify a novel mechanochemical pattern-generating motif, which represents the mechanism that drives the patterning of the PAR polarity proteins in the C. elegans zygote. Using Fluorescence Recovery After Photobleaching (FRAP) and RNA interference (RNAi), we demonstrate that the PAR domains feed back on the mechanics by establishing and maintaining a non-muscle myosin II (NMY-2) - based contractility gradient. To study the consequence of this PAR-mediated feedback on NMY-2, we first measured the dynamics of the PAR and NMY-2 system. Using calibrated, quantitative fluorescence microscopy, we measured the spatiotemporal evolution of the membrane-associated protein concentration of the posterior PAR-2, the anterior PAR-6 and NMY-2 as the mechanical force generator, as well as the cortical flow field. Next we show that these measured dynamics of PAR polarity establishment can be quantitatively recapitulated, using a reaction-diffusion-advection theory for the concentration fields of NMY-2, the posterior PAR-2 and the anterior PAR-6, in combination with a thin-film active-fluids theory for the flow field generated by NMY-2 gradients. Essential for this was the biochemical control of the PAR domains on the NMY-2 binding kinetics, which closes the mechanochemical feedback loop. Remarkably, our physical theory can, for the first time, fully recapitulate the spatiotemporal evolution of all the measured PAR-2, PAR-6 and NMY-2 membrane-concentration fields as well as the actomyosin flow field in the polarization process. We demonstrate that the function of this mechanochemical feedback is to amplify and stabilize cortical flows and thus to promote a rapid transition to the patterned state of the PAR system. We anticipate that this wok will open new avenues in our quantitative understanding of the emergence of patterns during the development of an organism.
Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The Genetics Society of America
9650 Rockville Pike, Bethesda, MD
Phone: 301-634-7300, Fax: 301-634-7079
Questions and Comments: firstname.lastname@example.org