Tissue growth constrained by extracellular matrix drives invagination during optic cup morphogenesis

Area of Science:

• Developmental Biology
• Biophysics
• Morphogenesis

Background:

• Embryonic eye development involves optic vesicle (OV) invagination to form the optic cup (OC).
• The precise mechanical mechanisms driving OV invagination remain incompletely understood.
• The role of the extracellular matrix (ECM) in this process is a key area of investigation.

Purpose of the Study:

• To investigate the hypothesis that the ECM mechanically constrains the developing optic vesicle, inducing invagination.
• To elucidate the specific stages of OV invagination where ECM interaction is critical.
• To understand the physical properties of the ECM and OV during morphogenesis.

Main Methods:

• Experiments in chick embryos involving removal of surface ectoderm (SE) at different developmental stages.
• Enzymatic disruption of the ECM using collagenase.
• Microindentation tests to measure the stiffness of the OV and ECM.
• Finite-element computational modeling of OV-ECM interaction.

Main Results:

• Removal of SE or disruption of ECM at early stages (HH14) caused OV to become convex ('pop out').
• At later stages (HH15), OV invagination proceeded even after SE removal, indicating reduced ECM dependence.
• Microindentation revealed the ECM is significantly stiffer than the OV.
• Computational models accurately reproduced experimental observations of OV curvature changes and invagination depth.

Conclusions:

• The ECM is essential for initiating optic vesicle invagination in early development.
• The mechanical constraint provided by a stiffer ECM is a primary driver of OV invagination.
• ECM properties, including differential stiffness, play a critical role in optic cup morphogenesis.