A Mechanical Role for Extracellular Matrix during Early Eye Morphogenesis
In the early embryo, the eyes form initially as relatively spherical optic vesicles (OVs) that protrude from both sides of the brain tube. Each OV grows until it contacts and adheres to the overlying surface ectoderm (SE) via extracellular matrix (ECM) secreted by the SE and OV. The OV and SE then thicken and bend inward (invaginate) to create the optic cup (primitive retina) and lens vesicle, respectively. While constriction of cell apices likely plays a role in SE invagination, the mechanisms that drive OV invagination are poorly understood.
We used experiments and computational modeling to explore the hypothesis that the ECM locally constrains the growing OV, forcing it to invaginate. In chick embryos, we tested this hypothesis by disrupting the matrix in two ways: (1) the SE was removed at different developmental stages and (2) the embryo was exposed to collagenase. At relatively early stages of invagination (Hamburger-Hamilton stage HH14-), removing the SE caused the curvature of the OV to reverse as it `popped out’ and became convex, but the OV remained concave at later stages (HH15). Disrupting the ECM had a similar effect, with the OV popping out at early to mid-stages of invagination (HH14- to HH14+). These results show that the ECM is required for the early stages but not the late stages of OV invagination. Microindentation tests confirmed that the matrix is considerably stiffer than the cellular OV, and a finite-element model consisting of a growing spherical OV attached to a relatively stiff layer of ECM reproduced the observed behavior, as well as measured changes in OV curvature, wall thickness, and invagination depth reasonably well. These results support our hypothesis, suggesting that ECM plays a major role in shaping the developing eye.
Bio
Larry Taber is the Dennis and Barbara Kessler Professor of Biomedical Engineering and Professor of Mechanical Engineering and Materials Science at Washington University in St. Louis. He moved to WU in 1997, after spending four years at the General Motors Research Laboratories and 15 years at the University of Rochester. Although his formal training is in aerospace engineering (B.A.E., Georgia Tech, 1974; Ph.D., Stanford University, 1979), he has published more than 100 journal articles on a wide range of topics including cochlear mechanics, nonlinear shell theory, cardiovascular mechanics, and the mechanics of growth and development. Ongoing research efforts integrate theoretical modeling with experiments on embryos to study the mechanics of heart, brain, and eye morphogenesis. Dr. Taber is a fellow of the American Society of Mechanical Engineers and the American Institute for Medical and Biological Engineering. Three times he has won the Richard Skalak Award for the best paper published in the Journal of Biomechanical Engineering (2004, 2007, 2015). Currently, he serves as co-editor-in-chief of the journal Biomechanics and Modeling in Mechanobiology.