Project 2B: Mechanochemical Control of Wound Healing in Developing Organs
Project 2B decodes mechanosensation and chemical signal integration during wound healing in developing animal organs. Objectives: (1) characterize effects of perturbing Piezo expression and function on cell/tissue mechanics in Drosophila wing disc; (2) investigate shared mechanisms of encoding information through second messenger signaling; (3) explore connections between mechanosensors and innate immune response.
Research Outputs
Piezo regulates epithelial topology and promotes precision in organ size control
Piezo identified as modulator of lateral inhibition in Drosophila wing development.
Figure 1. Piezo determines size precision in bilateral organs (A and A′) Drosophila wings from a Piezo-knockout line do not exhibit significant changes in average wing size compared to the control line used to generate the knockout line. (B and B′) Adult Drosophila wings generated using RNAi-mediated knockdown of Piezo and a previously validated corresponding control cross. (C and C′) Overexpression of Piezo in the wing disc results in smaller wings compared to control discs targeting a non-expressed gene with no observed phenotype. The reduction in wing area is visualized by comparing the outline of control wings (orange) with that of Piezo-overexpressed wings (green). (D) Piezo-knockout wings exhibit significant heterogeneity in wing size compared to the original Piggybac lines used to generate the knockout. Bee-swarm plot showing the distribution of wing area for different perturbations to Piezo. KO represents the Piezo-knockout line p value comparing means, and variances of populations are indicated over the solid lines. (E) Bee-swarm plot showing the quantified distribution of wing area for overexpression of Piezo. Superscripts I and II against the Piezo label indicate two different overexpression lines (detailed in the STAR Methods). Bonferroni correction was employed for statistical analysis. For an explanation of the bee-swarm plots, see Figure S2. (F and F′) Sister wings belonging to the control and Piezo-knockout lines demonstrate significant variation between bilateral organs. Red lines have been used to outline the contour of a sister wing. The same contour has been overlaid as dashed red lines for the other sister wing. All scale bars, 1 mm. (G) Bar graph showing the distribution of differences in the area between sister wings of the Piezo-knockout versus knockdown lines. (H) Adult UAS-RyrRNAi fly (control) and (H′) adult ap>PiezoRNAi fly showing significant patterning and symmetry defects between every two wings. Piezo knockdown (KD) caused (H′i) a tumorous and pigmentation phenotype and (H′ii) a less severe blister phenotype using two independent RNAi lines. See also Figures S1–S3.
Mim, M.S., et al. 2024. Piezo regulates epithelial topology and promotes precision in organ size control. Cell Reports, 43(7), 114398.
Reverse engineering morphogenesis through Bayesian optimization of physics-based models
Novel inverse modeling approach using Bayesian optimization for calibrating physics-based models.
Figure 1. a) Apical view of a z-projection of a Drosophila 3rd instar wing imaginal disc. B) Cross-section of the tissue along the anterior-posterior (AP) axis offset from the dorsal-ventral (D, V) boundary. c) The initial geometry used for Surface Evolver simulations. d) Definition of subcellular cytoskeletal interactions used to define the system's total energy. e) Minimum energy configuration obtained after optimization for parameters in Table 3. Note: The loss function measures the error between the experimental shape and the predicted shape from the model.
Kumar, N., et al. 2024. Reverse engineering morphogenesis through Bayesian optimization of physics-based models. npj Systems Biology and Applications, 10, 49.