Dr. T. J. Sego co-authored a research article with Sharon B. Minsuk, David M. Umulis, Mary C. Mullins, and James A. Glazier just published open-access in npj Systems Biology and Applications.
Abstract:
Morphogenesis in early development involves complex and extreme deformations in response to intra- and intercellular forces. Zebrafish epiboly, the spreading of the blastoderm to cover and engulf the large yolk cell, is a key early event that sets the stage for the establishment of the body plan, but the way the forces driving expansion are generated and mediated is poorly understood. The enveloping layer (EVL), the thin squamous outer epithelium of the blastoderm, plays a central role. Forces generated in the yolk cell are transmitted through tight junctions to the marginal EVL cells, and then propagate through the rest of the EVL. To understand mechanisms of force generation and transduction during epiboly, we first need a mechanical model of the EVL capable of responding to such forces and undergoing the drastic deformation of epiboly. The expanding EVL more than doubles its surface area and experiences significant shear as it deforms from a thin cap at one pole to become a complete sphere, necessarily requiring extensive internal rearrangement. We constructed an agent-based model of the EVL and its response to exogenous forces using the center-based simulation framework, Tissue Forge. Our model captures the large viscoelastoplastic deformation of the EVL by cell rearrangement, and accommodates the required cell neighbor exchanges without losing mechanical integration. Features observed in living embryos, such as the straightening of the initially ragged leading edge, also emerge in the model. We identified two key components required for realistic epiboly in the model: first, a mechanism to enable tissue remodeling by cell rearrangement without tearing the tissue, and second, a negative feedback on the forces driving EVL expansion, to regulate and synchronize the advancement of the EVL margin. We discuss the implications of these findings for the behavior of living EVL and the mechanisms that drive epiboly.
