@article {Robin076356, author = {Fran{\c c}ois B. Robin and Jonathan B. Michaux and William M. McFadden and Edwin M. Munro}, title = {Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo}, elocation-id = {076356}, year = {2016}, doi = {10.1101/076356}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Pulsed actomyosin contractility underlies diverse modes of tissue morphogenesis, but the mechanisms that generate pulsed contractions are still poorly understood. Here, we combine quantitative imaging with genetic perturbations and mathematical modeling to identify a core mechanism for pulsed contractility in early C. elegans embryos. We show that pulsed accumulation of actomyosin is governed almost entirely by local control of assembly and disassembly downstream of RhoA. Pulsed activation and inactivation of RhoA precedes, respectively, the accumulation and disappearance of actomyosin, and persists in the near complete absence of Myosin II. Autocatalytic activation of RhoA underlies rapid pulse initiation, while delayed accumulation of the RhoA GTPase activating proteins (GAPs) RGA-3/4 provides negative feedback to terminate each pulse. Mathematical models, tightly constrained by our experiments, confirm that this combination of positive and negative feedback is sufficient to generate locally pulsatile RhoA dynamics and reproduce the observed waveform of RhoA activation and RGA-3/4 accumulation. We propose that excitable RhoA dynamics are a common driver for pulsed contractility that can be tuned or coupled to actomyosin dynamics in different ways to produce a diversity of morphogenetic outcomes.ABanterior blastomere in the two-cell stage C. elegans embryoAHPHactive RhoA binding domain of AnillinGAPGTPase Activating ProteinNMY-2non-muscle myosin heavy chainP0one-cell C.elegans embryo, or zygoteTIRFtotal internal reflectionUTRF-actin binding domain of Utrophin}, URL = {https://www.biorxiv.org/content/early/2016/09/21/076356}, eprint = {https://www.biorxiv.org/content/early/2016/09/21/076356.full.pdf}, journal = {bioRxiv} }