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Together with first authors Paqui

G. Través and Lawrence Fourgeaud,

Lemke’s lab found that many more

living nerve cells were able to migrate

into the olfactory bulb (smell center)

in the absence of the receptors,

suggesting that Mer and Axl have

another role aside from clearing dead

cells: they may also target living, but

functionally compromised, cells. This

isn’t necessarily a bad thing: the brain

produces more neurons than it can use

and then prunes back the cells that

aren’t needed. However, in an inflamed

or diseased brain, the destruction of

living cells may backfire.

The team also looked at the receptors in

a mouse model of Parkinson’s disease

and found that afflicted mice missing

Axl andMer actually lived longer. This

may be because in the presence of

disease, there are more dysfunctional

neurons than normal and Axl andMer

may be prompting the destruction of

too many neurons, suggesting potential

new targets for treatment.

9

INSIDE SALK

SUMMER 2016

WWW.SALK.EDU

BRAIN GUARDIANS REMOVE DYING

NEURONS

An accumulation of dead cells (green spots) is

seen in the subventricular zone (SVZ) of the brain in

a mouse lacking the receptors Mer and Axl. (Blue

staining marks all cells.) No green spots are seen in

the SVZ from a normal mouse.

By adolescence, your brain

already contains most of

the neurons that you’ll have

for the rest of your life. But

a few regions continue

to grow new nerve cells—

and require the services

of cellular sentinels,

specialized immune cells

that keep the brain safe

by getting rid of dead or

dysfunctional cells.

Greg Lemke’s lab described the

surprising extent to which both dying

and dead neurons are cleared away

April 2016 in

Nature.

Previously, Lemke discovered

molecules called TAM receptors, two

of which (dubbedMer and Axl) help

immune cells that act as garbage

collectors to consume billions of dead

cells that are generated in a human

body every day.

The teamwondered if the receptors

did the same job in the brain. When

the researchers removed Axl andMer

from cells called microglia (responsible

for destroying pathogens in the brain)

in mice, they found that the absence

resulted in a large pile-up of dead cells,

but only in regions where the production

of new neurons is observed.

www.salk.edu/insidesalk0816/lemke