Differentiation of Human Embryonic Stem Cell (hESC) Derived Pyramidal Neurons

The mammalian cerebral neocortex is a complex six-layered structure containing multiple types of neurons. Pyramidal neurons of the neocortex are formed during development in an inside-out manner, by which deep layer (DL) neurons are generated first, and upper layer (UL) neurons are generated last. Neurons within the six-layered neocortex express unique markers for their position, showing whether they are subplate, deep layer, upper layer, or Cajal-Retzius neurons. The sequential generation of cortical layers, which exists in vivo, has been partially recapitulated in vitro by differentiation of mouse embryonic stem cells (Gaspard et al., 2008) and human embryonic stem cells (hESC) (Eiraku et al., 2008). The timeline of generation of cortical neurons from hESC is still not well defined, and could be very important in the future of cell therapy. In this study we will define timeline for UL and DL neurons for our experimental paradigm as well as test the effects of fibroblast growth factors (FGF) 2 and 8 on this neuronal differentiation. Recent papers suggest that FGFs are critical for forebrain patterning (Storm et al., 2003). Neuronal differentiation after treatment with either FGF2 or FGF8 from hESCs will be examined and the proportion of specific neuronal markers will be analyzed using immunocytochemistry. Our results show that the generated pyramidal neurons will express DL and UL laminar markers in vitro as they do in vivo and that the presence of FGF8 in induction media creates a proliferative effect, while FGF2 induces hESC to differentiate at a higher rate.

What Happens in the Links? Framing Judgment in Context

Scholars of Chaucer’s Canterbury Tales have focused much of their research on the interpretation of individual tales in the collection. The meaning behind these tales is clearly important to the work as a whole, as the Tales discuss grand themes that run throughout human life. The choice of themes and arguments in each pilgrim’s tale can also reflect back on the pilgrim’s own motivations and ideas. However, in searching for some greater meaning for Chaucer’s collection, it is important not to leave out the framework within which the tales exist. The links that join the tales to one another, arguably the portions of the piece that are the most original to Chaucer, do not always receive the same kind of attention that is focused on the most popular tales. In a work that is so complex, with its layered narration and interactions between tale and teller, the tales cannot possibly stand on their own, containing all of the meaning behind the work. The links have the potential to be particularly revealing in terms of how the audience should read the entire story of Chaucer’s Canterbury pilgrimage, because they ground the tales in specific circumstances.