Abstract
The eye has served as a classical model to study cell specification and tissue induction for over a century. Nevertheless, the molecular mechanisms that regulate the induction and maintenance of eye-field cells, and the specification of neural retina cells are poorly understood. Moreover, within the developing anterior forebrain, how prospective eye and telencephalic cells are differentially specified is not well defined. In the present study, we have analyzed these issues by manipulating signaling pathways in intact chick embryo and explant assays. Our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character, but from neural tube/optic vesicle stages, BMP signals from the lens are crucial for the maintenance of eye-field character, inhibition of dorsal telencephalic cell identity and specification of neural retina cells. Subsequently, our results provide evidence that a Rax2-positive eye-field state is not sufficient for the progress to a neural retina identity, but requires BMP signals. In addition, our results argue against any essential role of Wnt or FGF signals during the specification of neural retina cells, but provide evidence that Wnt signals together with BMP activity are sufficient to induce cells of retinal pigment epithelial character. We conclude that BMP activity emanating from the lens ectoderm maintains eye-field identity, inhibits telencephalic character and induces neural retina cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.
Highlights
During early development of the vertebrate central nervous system (CNS), the anterior neural domain becomes restricted into different regions, giving rise to the telencephalon, eye-field and hypothalamus
Strong expression of both FoxG1 and Emx2 marks the dorsal telencephalon, but no other regions of the forebrain (Fig. 1; supplementary material Fig. S2). These results show that neural retina cells can be distinguished from other eye and forebrain cell types by the co-expression of Rax2 and Vsx2 from early developmental stages
In agreement with our previous publications (Pandit et al, 2011; Sjödal et al, 2007), the generation of δ-crystallin+ lens cells was blocked by Bone morphogenetic protein (BMP) inhibition (Fig. 3A,B). These results suggest that BMP signals emanating from the prospective lens ectoderm are required for proper specification of neural retina cells, and in the absence of BMP activity, eye-field cells acquire dorsal telencephalic identity
Summary
During early development of the vertebrate central nervous system (CNS), the anterior neural domain becomes restricted into different regions, giving rise to the telencephalon, eye-field and hypothalamus (reviewed by Garcia-Lopez et al, 2009). The eye-field gives rise to most structures of the eye, such as the neural retina, the retinal pigment epithelium (RPE) and the optic stalk. The lens of the eye derives from the lens ectodermal placode (reviewed by Gunhaga, 2011). Whether the specification of eyefield cells and subsequent induction of neural retina cells occur in a single or distinct inductive event, and how this is regulated is not known. When and how neural retina cells are specified in relation to other eye and forebrain structures, and whether the prospective lens plays any role in this process, remain to be examined.
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