1088-B 6 MARCH 2020 • VOL 367 ISSUE 6482 sciencemag.org SCIENCE
RESEARCH
DEVELOPMENT
Paths to understanding
breastmilk
Breastfeeding is important for
infant and maternal health.
Some of the mechanisms that
account for the benefits of
breastmilk include improved
nutritional and immune status,
but much is still unknown about
how breastmilk confers health
benefits. In a Perspective,
Bode et al. discuss paths to
understanding the mother-
breastmilk-infant triad. They
focus on how improved knowl-
edge of the triad could inform
research on two key issues
for infant health: childhood
undernutrition and necrotizing
enterocolitis, a fatal gastroin-
testinal disorder that affects
preterm infants. —GKA
Science, this issue p. 1070
GERM CELL DEVELOPMENT
Commencing oogenesis
In mice, embryonic stem cells
and induced pluripotent stem
cells have been shown to dif-
ferentiate into primordial germ
cell–like cells that can give rise
to functional oocytes. In this
system, Nagaoka et al. identified
the gene Zglp1 as a necessary
and sufficient factor for confer-
ring the oogenic fate to sexually
undetermined germ cells. As a
downstream effector of bone
morphogenetic protein signal-
ing, conserved transcriptional
regulator ZGLP1 activates the
oogenic program repressed by
Polycomb activities, whereas
retinoic acid signaling assists the
maturation of such activation
and also the repression of the
primordial germ cell program.
This study thus refines our
understanding of mammalian
oogenic fate determination.
—BAP
Science, this issue p. 1089
INTEGRATIVE OMICS
Mapping the
mammalian brain
The diverse physiology of the
brain is reflected in its complex
organization at regional, cellular,
and subcellular levels. Sjöstedt
et al. combined data—both
newly acquired and from other
large-scale brain mapping
projects—from transcriptomics,
single-cell genomics, in situ
hybridization, and antibody-
based protein profiling to map
the molecular profiles in human,
pig, and mouse brain. The
analysis is consistent with a con-
served basic brain architecture
during mammalian evolution,
but it does show differences
in regional gene expression
profiles. —VV
Science, this issue p. 1090NEUROSCIENCE
A major psychosocial
stress circuit
Psychological stress induces
various physiological responses
by activating the sympathetic
nervous system. The brain cir-
cuits involved in these functions
are still not completely under-
stood. In a rat model, Kataoka et
al. combined anatomical tracing,
immediate early gene expres-
sion analysis, pharmacology,
optogenetics, electrophysiol-
ogy, and genetic cell ablation
to provide evidence for the
prominent role of a ventral part
of the medial prefrontal cortex in
sympathetic responses to social
defeat stress. This brain region
sends excitatory projections to
the dorsomedial hypothalamus
as a central coordinator of the
psychosocial stress responses.
This pathway is crucial for
understanding how psychosocial
stress influences a variety of
body functions. —PRS
Science, this issue p. 1105LIQUID CRYSTALS
Watching defects
flow and grow
Orientational topological defects
in liquid crystals, known as
disclinations, have been visual-
ized in polymeric materials or
through mesoscale simulations
of the local orientation of the
molecules. Duclos et al. report
the experimental visualization
of the structure and dynamics
of disclination loops in active,
three-dimensional nematics
using light-sheet microscopy
to watch the motion of nematic
molecules driven by the motion
of microtubule bundles (see
the Perspective by Bartolo).
This setup makes it possible to
directly watch the nucleation,
deformation, recombination, and
collapse of spatially extended
topological defects in three
dimensions. —MSL
Science, this issue p. 1120;
see also p. 1075MICROBIOLOGY
Porin’ through the wax
Mycobacterium tuberculosis
has a distinctive physiology that
allows it to persist in the human
body, including a wax-like cell
coat that is largely imperme-
able and can resist attack by
host immune response effec-
tors. Wang et al. identified a
simple molecule that effectively
crosses this cell coat and kills
M. tuberculosis cells. Whole-
genome sequencing of mutants
resistant to this molecule, 3,3-bis-
di(methylsulfonyl)propionamide,
showed scattered mutations in a
protein called PPE51, and these
mutants resulted in a spec-
trum of nutrient-related growth
defects. Experiments suggest
that PE/PPE family proteins
are small molecule–selective
channels analogous to outer
membrane porins, which allow M.
tuberculosis to take up nutrients
while maintaining an otherwise
impermeable barrier. —CA
Science, this issue p. 1147CANCER
Palmitoylation makes
the switch for EGFR
Aberrant epidermal growth
factor receptor (EGFR) signaling
through two important path-
ways, RAS–mitogen-activated
protein kinase (RAS-MAPK) and
phosphatidylinositol 3-kinase
(PI3K), promotes tumor growth.
EGFR inhibitors are rarely effec-
tive in tumors with mutations
in the protein KRAS, which
stimulate the MAPK pathway
independently of EGFR activ-
ity. Kharbanda et al. found
that EGFR palmitoylated on
the intracellular tail interacted
preferentially with a PI3K subunit
rather than a MAPK adaptor
protein. Blocking palmitoylation
reduced PI3K signaling activ-
ity and sensitized cells to PI3K
inhibitors. These results explain
why EGFR inhibitors are effective
only in cancer cells in which
EGFR is palmitoylated.
—LKF
Sci. Signal. 13 , eaax2364 (2020).THYMUS
PAX1 in the thymus
Severe combined immunode-
ficiency encompasses a wide
spectrum of genetic disorders.
Yamazaki et al. studied immune
deficits in six patients with
otofaciocervical syndrome
type 2, a genetic abnormality
attributed to biallelic mutations
in the transcription factor PAX1.
In addition to immunodeficiency,
the disease is also characterized
by facial dysmorphism, hearing
loss, and skeletal abnormalities.
The patients were subjected
to hematopoietic stem cell
transplantation to rectify their
immunodeficiency. Despite
successful engraftment in three
of the patients, all three failed
to develop T cells. By generat-
ing patient-derived induced
pluripotent stem cells and
differentiating them ex vivo into
thymic epithelial progenitor
(TEP) cells, the authors found
that PAX1 plays an importantEdited by Michael FunkALSO IN SCIENCE JOURNALS
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