London: The processes involved in the formation of complex tissues and organs are still a mystery in science.
However, Japanese researchers have made a major breakthrough in the creation of retinal optic tissue using embryonic mouse stem cells.
The discovery answers important questions as to whether signalling interactions between neighbouring tissues are essential for guiding organogenesis, or whether these can arise autonomously from developmental routines inherent to a given primordial tissue.
The formation of the optic cup, with its complex two-walled structure, has been a longstanding question in embryology.
The retina, with its origins in the lateral midbrain, is part of the central nervous system. Its development begins with the formation of the optic vesicle, a pocket of epithelium that deepens and pinches to form the optic cup, which develops a double layer of cells, with pigment epithelium on the outer, and neural retina on the inner wall.
Some believe that this transformation is triggered by chemical and physical influences from other tissues, such as lens or cornea, but others have suggested that perhaps external induction or force is not required.
To resolve this important question, Mototsugu Eiraku , deputy leader of the Four-dimensional Tissue Analysis Unit, and his colleagues used techniques based on an embryonic stem cell culture system developed by Sasai lab.
These techniques had previously been used to differentiate pluripotent stem cells into a wide range of neuronal cell types, including structurally organized cerebral cortical neurons.
By adding extracellular matrix proteins to the culture, the group was able to epithelially-organize retinal precursors at high efficiencies by day 7.
One day later, optic vesicle-like structures began to form, followed by bi-layered optic cup-like structures (day 10).
The pigmented and neuronal characters of the outer and inner layers of cells in these spontaneously formed tissues were confirmed by gene expression, indicating that optic cup development had been successfully generated in vitro.
Most importantly, the tissue had developed in the absence of any external signaling sources, thus demonstrating the capacity for self-organization.
They next used multi-photon microscopy to explore the mechanisms behind this process of self-assembly in 3D. They found that after the ES cell-derived retinal precursors differentiated into pigmented epithelial and neuronal layers, the tissue underwent a four step morphological rearrangement on its way to assuming the optic cup structure.
"What we`ve been able to do in this study is resolve a nearly century-old problem in embryology, by showing that retinal precursors have the inherent ability to give rise to the complex structure of the optic cup," said Sasai.
The finding is detailed in Nature.