Did HARE5 blew the WNT of change in Adam’s brain?

Okay, it is surely a lousy wording from me but it’s all about these “brainiac” mice that have shown an enlarged brain, in particular in their neocortex (a brain region associated with high cognitive and social task processing).
In the study by Boyd and colleagues published in Current Biology entitled “Human-Chimpanzee Differences in a FZD8 Enhancer Alter Cell-Cycle Dynamics in the Developing Neocortex: Current Biology“, the authors have inserted a particular DNA region called HARE5 into mice and observed the expression of this genomic sequence during development using the classical LacZ reporter. For those who do not know about LacZ, it is an enzyme that is expressed in bacteria such as E.coli that breakdown lactose into glucose and galactose (a close cousin of the same enzyme that make you lactose-tolerant or intolerant). The good thing about this tool for biologist is that it can act as a great tracer to screen when and where a gene is turned ON. Once ON, this gene is transcript into messenger RNA and then translated into proteins (central dogma, Biology 101 anyone?). Then you can track the enzyme activity with a chromogenic substrate, in this case X-gal. X-gal gets cleaved by LacZ (because LacZ may think it is a lactose) and release the X from the gal, giving a nice indigo blue color like the picture below:

If you place a DNA sequence that you think acts as a promoter for a gene, just stick it next to the LacZ gene, insert into your embryos and track it down during different developmental stage (a mouse have about 22 days of gestation).
Now what it is interesting is that the authors pinned HARE5 as an interesting candidate, as it enlarged mouse brain in HARE5 transgenic mice compared to wild type. But this enlargement was only present in transgenic mice containing the human HARE5 sequence not the chimp one, bringing the speculation very high about this sequence on the evolution of Adam’s brain from our chimp far-distant cousins. It would be interesting to track back in time how the “lucky winner” individual diverged the road from our common ancestor and how that sequence among the human and non-human primates.
The second thing that was really exciting was the possible candidate driven by HARE5: FZD8. FZD8 denotes “Frizzled 8”, a important receptor of the WNT/beta-catenin pathway that appears to share important role in both neuronal cell differentiation AND the blood-brain barrier differentiation. I am very excited to see how this HARE5 may impact the blood-brain barrier function of these animals. Do these animals have a better BBB tightness, a higher vascular density, a different in nutrient uptake (there is a lot of speculation about the DHA transporter and DHA (aka Omega-3 fatty acid) in our brain homeostasis.
Lets see now how these puppies perform in behavioral tests….


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