Rewired brain: Faulty autism gene may affect expression of other genes

brain

TBR1 is among a select set of genes with strong ties to autism. The new findings explain that connection: Mutations in TBR1 may disrupt gene expression in a way that alters brain circuits.

When the gene is disabled in layer 6 — the deepest layer — of the cerebral cortex of mice at birth, the neurons there do not wire up the way they typically do.

[The researchers] created two sets of mice with mutations in TBR1 only in layer 6. Some of the mice have no TBR1; others lack just one copy, akin to what happens in people with a TBR1 mutation. In both cases, the approach enables researchers to curtail TBR1 expression starting around birth.

Looking in the brains of these mice, the researchers found that many of the dendrites — the signal-receiving branches of neurons — of layer 6 neurons extend to layer 1, which is typical of layer 5 neurons. “That never happens in normal layer 6 neurons,” [researcher John] Rubenstein says.

Related article:  Harmless mutations may cause serious illnesses when combined together, case study shows

These dendrites also form significantly fewer connections, or synapses, with other neurons than typical layer 6 neurons do.

The researchers used viruses to deliver functional versions of the four genes involved in synapse formation to both sets of mutant mice. One of these replacements, WNT7b, restores the number of synapses to the typical number. “That’s exciting, because it opens the possibility to think about therapy for at least the TBR1 type of autism,” Rubenstein says.

Read full, original post: Top autism gene may rewire brain by altering expression of other genes

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