RT Journal Article
SR Electronic
T1 Epithelial organ shape is generated by patterned actomyosin contractility and maintained by the extracellular matrix
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.22.915272
DO 10.1101/2020.01.22.915272
A1 Ali Nematbakhsh
A1 Megan Levis
A1 Nilay Kumar
A1 Weitao Chen
A1 Jeremiah Zartman
A1 Mark Alber
YR 2020
UL http://biorxiv.org/content/early/2020/01/23/2020.01.22.915272.abstract
AB Epithelial sheets play important roles in defining organ architecture during development. Here, we employed an iterative experimental and multi-scale computational modeling approach to decouple direct and indirect effects of actomyosin-generated forces, nuclear positioning, extracellular matrix (ECM), and cell-cell adhesion in shaping Drosophila wing imaginal discs, a powerful system for elucidating general principles of epithelial morphogenesis. Basally generated actomyosin forces are found to regulate apically biased nuclear positioning and are required for generating epithelial bending and cell elongation of the wing disc pouch. Surprisingly, however, short-term pharmacological inhibition of ROCK-driven actomyosin contractility does not impact the maintenance of tissue height or curved shape. In comparison, the relative tautness of the extracellular basement membrane is also patterned between regions of the wing disc. However, computational simulations show that patterning of ECM tautness provides only a minor contribution to modulating tissue shape. Instead, the buildup of a passive ECM pre-strain serves a principle role in shape maintenance. Surprisingly, this is independent from the maintenance of actomyosin contractility. Furthermore, localized apical adhesion between the two cell layers within the wing disc requires ROCK-driven actomyosin activity in the absence of the basal extracellular matrix. This apical adhesion between the two cell layers provides additional mechanical support to help maintain tissue integrity. The combined experimental and computational approach provides general insight into how the subcellular forces are generated and maintained within individual cells to induce tissue curvature and suggests an important design principle of epithelial organogenesis whereby forces generated by actomyosin followed by maintenance as pre-strain within the ECM are interconnected, but functionally separable.Significance statement A major outstanding question in developmental biology is the elucidation of general principles of organ shape formation and maintenance. Here, an iterative experimental and multi-scale computational modeling approach reveals that actomyosin contractility generates the bent profile along the anterior-posterior axis while tension within the ECM is sufficient and necessary for preserving the bent shape even in the absence of continued actomyosin contractility once the shape is generated. The mechanisms tested in this study define the necessary factors for establishing the shape of the wing disc, which later everts to form the adult wing during pupal development. The method can be extended to test novel mechanisms of other epithelial systems that consist of several cellular and ECM layers.