Cell - 8 September 2016

(Amelia) #1

shows weaker SIM binding, supporting a
model in which dissociation of CPR5 ho-
momeric binding releases CKIs during
ETI and drives E2F-controlled gene
expression. Notably, SIM overexpression
is not sufficient in isolation to cause full
ETI activation, indicating that both CKI
release and structural changes within the
NPC are essential for immune responses.
ArabidopsisSIM and SMR1 are impor-
tant for the control of endoreplication
(Churchman et al., 2006), which facilitates
the formation of specialized cells through
multiple rounds of replication without
intervening cell division. SIM is particu-
larly critical for the development of tri-
chomes, branched single-celled shoot
hairs that extend out from the epidermis.
CPR5 has been implicated in a wide
variety of developmental pathways, in-
cluding endoreplication of trichomes. It
will be fascinating in the future to examine
whether the CPR5 oligomeric changes
may also come into play in these con-


texts, regulating SIM and SMR1 function
in other endoreduplicating cells.
Overall,Gu et al. (2016)have revealed a
novel signaling mechanism employing the
NPC as a versatile regulatory platform
that will likely impact our understanding
of immune and cell death pathways not
only in plants but also in mammals. Future
structural studies in this context may
uncover the plasticity of the nuclear pore
under pathogen challenge.

ACKNOWLEDGMENTS

We thank Angela Diehl for the illustration. M.D. is
supported through NICHD Intramural Project
#Z01 HD008954. B.M.A.F. is supported by: NIH
R01 GM113874-01; R01AI125524-01; and R21
AI119304-01.

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Cell-Type-Specific Optogenetics in Monkeys


Vijay Mohan K. Namboodiri1,2and Garret D. Stuber1,2,3,*


(^1) Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
(^2) Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
(^3) Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
*Correspondence:[email protected]
http://dx.doi.org/10.1016/j.cell.2016.08.047
The recent advent of technologies enabling cell-type-specific recording and manipulation of
neuronal activity spurred tremendous progress in neuroscience. However, they have been largely
limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a gener-
alizable method for achieving cell-type specificity in monkeys.
The last decade has been transformative
for neuroscience. This is primarily due to
the advent of exciting technologies that
permit monitoring and manipulation of
specific neural circuits (Deisseroth and
Schnitzer, 2013). While neural circuits
were traditionally considered to have no-
des representing different anatomical
areas, a preponderance of evidence now
suggests that these nodes are formed
by specific cell types within areas—
defined by genetic markers or projec-
tions—instead of the areas as a whole.
Thus, it is vital that future work strives to
define and study precisely defined cell
types. However, most mammalian studies
have relied on mice, which lack the
complex behavioral repertoire that other
species such as rats, and especially
monkeys, possess. Thus, being able to
perform cell-type-specific studies in mon-
keys would be a major leap in the prog-
ress of neuroscience. In this issue of
Cell,Stauffer et al. (2016)present the
first such study in monkeys by targeting
midbrain dopamine neurons for both
optogenetic tagging and manipulation.
Historically,methodsfor cell-typespec-
ificity have relied heavily on genetically
modified ‘‘lines,’’ especially mice, fish,
and flies (Capecchi, 2005; Miklos and
Rubin, 1996). Specifically, neuroscientists
have made use of animals in which
DNA has been added or modified within
the genome in embryonic stem cells.
These techniques have been greatly
1366 Cell 166 , September 8, 2016ª2016 Elsevier Inc.

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