THE ROLE OF THE CYTOSKELETON IN THE DEVELOPMENT OF THE OPTIC VESICLE

An ultrastructural, topographical, and histological study of the normal cell shaping changes which occur during the formation of the optic vesicle was carried out. The role of the cytoskeleton was also tested by exposing mouse embryos to drugs which specifically inhibited microtubules (vincristine sulfate) or microfilaments (cytochalasin B).;Correlated in vivo and in vitro experiments demonstrated direct and indirect effects of cytoskeletal active agents on the optic vesicle cells. Light, transmission electron and scanning electron microscopy methods were used to examine the morphological changes caused by inhibiting microtubule and microfilament function.;Vincristine sulfate deleteriously affected optic vesicle and cephalic neural tube formation in vivo and in vitro. The developmental stage of the embryo at the time of exposure in vitro correlated with the degree of maldevelopment of the optic vesicle. Embryos exposed in vitro at earlier stages (1-3 somite) were more severely affected than embryos exposed at later stages (4-6 somites).;Cytochalasin B also caused malformations of the optic vesicles and neural tube in vitro. The neuroepithelial cells failed to elevate and become wedge shaped. The optic vesicle also failed to invaginate from the prosencephalon. The embryos exposed to cytochalasin B in vivo were less severely affected, indicating the drug may not have reached the fetal compartment in a large enough dose to cause severe malformations of the optic vesicle.;The early formation of the optic anlagen occurs during a highly circumscribed period of development in the mammalian embryo. During this time, it was demonstrated that in the optic primordia, the cells increase their length by one and one-half times and decrease in apical width by half. The cell shaping changes correlate with the appearance of microtubules before cell elongation and the increase of microfilament bundle density prior to the cell apices becoming constricted.;As hypothesized, interference with microtubules or microfilaments with vincristine sulfate or cytochalasin B respectively inhibited normal formation of the optic vesicle.