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A change in Pax6 gene expression allows neural progenitor cells in mice embryos to undergo multiple rounds of cell division, and increases the number of neurons in the neocortex:
The developing neocortex contains different types of neural stem and progenitor cells, but one particular class, the basal progenitors, behave differently in small-brained animals such as mice than in large-brained animals such as humans. In humans, basal progenitors can undergo multiple rounds of cell division, thereby substantially increasing neuron number and ultimately the size of the neocortex. In mice, these progenitors typically undergo only one round of cell division, thus limiting the number of neurons produced. A potential cause underlying this difference in the proliferative capacity of basal progenitors could be the differential expression of Pax6 between species. Mouse basal progenitors, in contrast to human, do not express Pax6. "We were very curious to see what would happen if we were to change the expression pattern of Pax6 in developing mouse brain to mimic that observed in large-brained animals", says Fong Kuan Wong, a PhD student in the lab of Wieland Huttner and first author of the [open access] study.
To this end, another PhD student in the lab, Ji-Feng Fei, generated a novel transgenic mouse line. This line provided the basis for altering the expression of Pax6 in the cortical stem cell lineage such that it would be sustained in basal progenitors. The researchers then introduced the Pax6 gene into the stem cells of these mouse embryos. Strikingly, sustaining Pax6 expression in mouse basal progenitors increased their capacity to undergo multiple rounds of cell division, as typically observed in primates. This not only expanded the size of the basal progenitor population in a way somewhat reminiscent to what is seen in large-brained animals. It also resulted in an increase in cortical neurons, notably those in the top layer, another characteristic feature of an expanded neocortex.
(Score: 1, Interesting) by Anonymous Coward on Wednesday August 12 2015, @01:56AM
I've been trying to offer alternative explanations for the bio articles posted here, but this paper is too long (44 pages). There is a lot of histology going on there. However, they also do a lot of normalizing to red fluorescent protein: "all our quantifications are confined to electroporated, RFP-positive cells".
Perhaps the denominator is changing rather than the numerator? From figure 2E it looks like there may be some effect of Pax6 on RFP expression, but that data is still in normalized form. I think we need the total unnormalized RFP comparisons which I did not see. Any ideas?
(Score: 0) by Anonymous Coward on Wednesday August 12 2015, @05:04AM
It doesn't look like there is much of a difference. The plasmids share the same promoter so the RNA levels should be about the same and the RFP is independently translated through the IRES element.
Or do you think there is a difference in transfection efficiency? The Pax6 plasmid would be a bit larger but probably wouldn't change the efficiency too much.
(Score: 0) by Anonymous Coward on Wednesday August 12 2015, @05:24AM
I'm not sure how it would all work out in vivo, co-expressing Pax6 and RFP could also affect degradation of RFP, etc. The idea is that if the co-expression increases RFP fluorescence somehow then it would make it appear that there was less of whatever other protein they are normalizing to RFP, and vice versa. In principle, it could even have opposite effects in different areas or cell types. This would be pretty easily addressed by reporting the raw signals used for each normalization, which I don't *think* that they share. As I said, long paper, but I consider this a standard concern about normalized data.