Defects in chicken neuroretina misexpressing the BMP antagonist Drm/Gremlin

During eye development, bone morphogenetic proteins (BMPs) exert multiple actions on both early and late patterning and differentiation processes. However, the roles of BMP signaling in retinal differentiation are not well understood. To gain insight into a novel role of BMPs during retinal development, we proceeded to retrovirally directed misexpression of the BMP antagonist Drm/Gremlin in the chicken optic vesicle. This resulted in severe eye defects, characterized by microphthalmia, coloboma and the presence of dark streaks. The latter phenotype corresponds to localized perturbations of the stratified structure of the neuroretina. We show that these retinal disorganizations are characterized by a destruction of neuronal layers associated with axonal pathfinding defects, increased apoptosis and lost of N-cadherin expression. Moreover, whereas neuronal differentiation seems to proceed normally, Müller glial differentiation is impaired in Drm-induced disorganizations. These data suggest a possible role of BMP signaling in the laminar organization of the developing neuroretina.