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Effects of Microcephaly-Linked Gene Mutation Studied in Ferrets

Accepted submission by takyon at 2018-04-15 20:13:05

Mutant ferrets offer clues to human brain size []

By inactivating a gene linked to abnormally small brain size in humans, researchers have created the first ferret with a neurological mutation. Although the original impetus of the work was to study human brain disease and development, says Howard Hughes Medical Institute (HHMI) Investigator Christopher Walsh, the results also shed light on how the human brain expanded during the course of evolution.

[...] Walsh, Bae, and their colleagues discovered that their ferrets model human microcephaly much more accurately than do mice. The ferrets displayed severely shrunken brains, with up to 40 percent reduced brain weight. And, as in humans with the condition, cortical thickness and cell organization were preserved.

What's more, the ferrets reveal a possible mechanism for how human brains have grown over evolutionary time. Over the last seven million years, human brain size has tripled. Most of this expansion has occurred within the cerebral cortex. Indeed, in the mutant ferrets, researchers traced the cerebral cortex deficits to a type of stem cell called outer radial glial cells (ORGs). ORGs are created by stem cells capable of making all sorts of different cells in the cortex. Walsh's team found that Aspm [a gene linked to microcephaly in humans] regulates the timing of the transition between these stem cells and ORGs. This affects the ratio of ORGs to other types of cells. Thus, tweaking Aspm can actually dial up or down the number of nerve cells in the brain, Walsh says, without having to change many genes all at once.

Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size [] (DOI: 10.1038/s41586-018-0035-0) (DX [])

Original Submission