ABSTRACT
Morphogenesis is the process whereby the body of an organism develops its target shape. The morphogen BMP is known to play a conserved role across bilaterian organisms in determining the dorsoventral (DV) axis. Yet, how BMP governs the spatio-temporal dynamics of cytoskeletal proteins driving morphogenetic flow remains an open question. Here, we use machine learning to mine a morphodynamic atlas of Drosophila development, and construct a mathematical model capable of predicting the coupled dynamics of myosin, E-cadherin, and morphogenetic flow. Mutant analysis shows that BMP sets the initial condition of this dynamical system according to the following signaling cascade: BMP establishes DV pair-rule-gene patterns that set-up an E-cadherin gradient which in turn creates a myosin gradient in the opposite direction through mechanochemical feedbacks. Using neural tube organoids, we argue that BMP, and the signaling cascade it triggers, prime the conserved dynamics of neuroectoderm morphogenesis from fly to humans.
ABSTRACT
Morphogenesis is the process whereby the body of an organism develops its target shape. The morphogen BMP is known to play a conserved role across bilaterian organisms in determining the dorsoventral (DV) axis. Yet, how BMP governs the spatio-temporal dynamics of cytoskeletal proteins driving morphogenetic flow remains an open question. Here, we use machine learning to mine a morphodynamic atlas of Drosophila development, and construct a mathematical model capable of predicting the coupled dynamics of myosin, E-cadherin, and morphogenetic flow. Mutant analysis shows that BMP sets the initial condition of this dynamical system according to the following signaling cascade: BMP establishes DV pair-rule-gene patterns that set-up an E-cadherin gradient which in turn creates a myosin gradient in the opposite direction through mechanochemical feedbacks. Using neural tube organoids, we argue that BMP, and the signaling cascade it triggers, prime the conserved dynamics of neuroectoderm morphogenesis from fly to humans.
ABSTRACT
Organ development involves complex shape transformations driven by active mechanical stresses that sculpt the growing tissue 1,2. Epithelial gland morphogenesis is a prominent example where cylindrical branches transform into spherical alveoli during growth3-5. Here we show that this shape transformation is induced by a local change from anisotropic to isotropic tension within the epithelial cell layer of developing human mammary gland organoids. By combining laser ablation with optical force inference and theoretical analysis, we demonstrate that circumferential tension increases at the expense of axial tension through a reorientation of cells that correlates with the onset of persistent collective rotation around the branch axis. This enables the tissue to locally control the onset of a generalized Rayleigh-Plateau instability, leading to spherical tissue buds6. The interplay between cell motion, cell orientation and tissue tension is a generic principle that may turn out to drive shape transformations in other cell tissues.
