Michalis Agathocleous, Nicola K. Love, Owen Randlett, Julia J. Harris, Jinyue Liu, Andrew J. Murray and William A. Harris have published a very interesting story on proliferating cells of the Xenopus laevis retina that documents aerobic glycolysis rather than oxidative phosphorylation. Historically, this shift in metabolism was termed the Warburg effect where it was originally described in tumorigenesis. Could it be that this shift in metabolism is more widely used than previously anticipated? Certainly in the proliferating developing Xenopus laevis retina, it appears so, even in the presence of oxygen. The only other instance of aerobic glycolosis I am aware of is in T-cells, but that too is associated with oncogenicity.
This really opens up possibilities for metabolic control of a variety of processes in not only development, but also pathology with respect to alternative methods for defining metabolic states and deriving energy.
I was blown away by this paper out of the Sasai laboratory at the Riken Center for Developmental Biology. Essentially, the Sasai laboratory is trying to recapitulate the developmental process of the retina in a test tube in isolation from the rest of the live animal. Its a stunning development that appears to demonstrate bilayered optic vesicles, then cups that reach around to surround the lens vesicle. Many efforts to grow organs in a dish have been attempted before, going back to the 1990’s, and eye development studies have been performed in frogs to get eyes to grow in places they do not normally develop, but this is the first time such a complex tissue/organ has been apparently successfully demonstrated in culture conditions. The advance from the Sasai laboratory specifically demonstrates that the evagination of the optic vesicle can be induced and controlled to form a bilayered cup (from this Webvision page, animation here). This process normally requires the surrounding tissues to provide guidance and induction cues, so engineering this to happen spontaneously from homogeneous pluripotent cells in culture is a substantial advance.
Continue reading “Notable Papers: Self-organizing optic-cup morphogenesis in three-dimensional culture”