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Development 139 (21)
During development, competitive interactions between
embryonic cells influence their ability to contribute to the
adult. Specifically, faster-growing cells (‘winners’) induce
apoptosis in nearby slower-growing cells (‘losers’). In
Drosophila, Myc regulation, ribosome biogenesis and Wingless signalling have
all been implicated in cell competition. Erika Bach and colleagues now add
JAK/STAT signalling to the list of cell competition regulators (see p. 4051). The
researchers show that Drosophila wing imaginal disc cells that lack STAT
become losers that are killed by neighbouring wild-type cells. By contrast, cells
with hyperactivated STAT become supercompetitors that kill wild-type cells
located several cell diameters away through induction of apoptosis.
Importantly, the researchers also report that STAT-dependent cell competition
does not require Myc, Yorkie (part of the Hippo pathway that feeds into Myc
regulation), Wingless signalling or ribosome biogenesis. Thus, the researchers
suggest, STAT, Wingless and Myc are parallel regulators of cell competition in
Drosophila (and possibly in other organisms), which may converge on signals
that non-autonomously kill losers.
EpiSC model for anterior neural
plate development
Somatic lineages in amniotes are derived from the
epiblast but little is known about the cell-intrinsic
transcriptional regulation of somatic lineage generation.
Here (p. 3926), Hisato Kondoh and colleagues use
mouse epiblast stem cell (EpiSC) lines to remedy this situation. By comparing
the transcription factor expression profiles of embryonic tissues with those of
EpiSCs cultured for one day in the absence of the extrinsic signals needed to
maintain their epiblast state, the researchers show that the immediate
derivatives of EpiSCs under these conditions represent the anterior neural plate
(ANP) state in ~E7.5 embryos. They then analyse the effects of knockdown and
overexpression in EpiSCs of transcription factors that exhibit uniform
expression in the E6.5 epiblast but localised expression within or external to
the ANP. These analyses indicate that intricate cross-regulation among Zic,
Otx2, Sox2 and Pou factors stabilises the epiblast state and generates the ANP.
Overall, this study highlights the advantages of EpiSCs for studies of somatic
lineage derivation.
Mice develop without maternal Cdx2
Maternal genes, which are transcribed in the female
germline during oogenesis, play variable roles in
embryonic patterning. In frog embryos, for example,
differentially localised maternal factors regulate early cell
fate decisions. By contrast, the contribution of maternal factors to mammalian
embryo patterning remains controversial. On p. 3969, Amy Ralston and coworkers re-examine the requirement for maternal Cdx2 (the orthologue of the
Drosophila maternal-effect gene caudal) during mouse development. Previous
studies that used RNA interference (RNAi) to reduce Cdx2 levels have yielded
contradictory results about the requirement for maternal Cdx2 during mouse
development. This lack of agreement might have arisen because injection of
RNAi constructs can introduce experimental variation. Therefore, to
unambiguously resolve this issue, Ralston’s team used a Cre/lox strategy to
genetically ablate Cdx2 in oocytes before fertilisation. Their approach, which
involved three generations of crosses and over 25 weeks of breeding, allowed
them to determine that neither trophectoderm cell polarity nor initial cell fate
depends on maternal Cdx2. Thus, they conclude, maternal Cdx2 is dispensable
for mouse development.
Sox1 makes a mark on
neurogenesis
Neurogenesis occurs within the subgranular zone
(SGZ) of the dentate gyrus of the mammalian brain
throughout life. However, the nature of the neural
stem cells (NSCs) that produce mature granular neurons remains
controversial, in part because of a lack of NSC markers. Now, on p. 3938,
Robert Blelloch and colleagues identify the transcription factor Sox1 as a
potential NSC marker. The researchers use real-time reporters and lineage
tracing to show that a subset of radial astrocytes in the SGZ expresses Sox1
and gives rise to nearly all newly born granular neurons. After 8 weeks of
labelling and a 12-week chase, the researchers report, up to 44% of the
granular neurons in the dentate gyrus are derived from Sox1 lineage-traced
cells. Moreover, although the proportion of Sox1-positive cells in the radial
astrocyte population decreases with age, these cells remain
transcriptionally stable throughout the lifetime of the mouse. Together,
these results suggest that Sox1 marks a population of activated neural
stem/progenitor cells in the mouse hippocampus.
Pancortin-APP interactions
modulate neural migration
Neuronal precursor cell (NPC) migration in the
developing mammalian brain requires the coordinated
interaction of many factors. One factor involved in NPC
migration into the cortical plate is the transmembrane glycoprotein amyloid
precursor protein (APP), which is also involved in the pathogenesis of
Alzheimer’s disease. However, the extracellular factors that signal through APP
to regulate migration are unknown. Now, in a mass spectrometry screen, Tracy
Young-Pearse and co-workers (p. 3986) identify pancortins (secreted
glycoproteins that are expressed throughout the developing and mature
cerebral cortex) as factors in mouse brain that bind to the extracellular domain
of APP. APP interacts with all four mammalian pancortin isoforms, the
researchers report. Moreover, in vivo loss- and gain-of-function experiments
in rats reveal that pancortins are involved in NPC migration into the cortical
plate, with different isoforms having opposing roles in this process. These and
other results reveal new roles for pancortins in mammalian cortical
development and provide novel insights into the physiological function of APP.
Molecular insights into senescence
All eukaryotes undergo senescence (time-related
deterioration of physiological functions). For most organisms
this process is irreversible but, on p. 4083, Kaz Kawamura
and co-workers report that in the asexual strain of the
tunicate Polyandrocarpa misakiensis several ageing processes
are reversible. P. misakiensis propagates by budding; the resultant zooids
release buds themselves before dying after a lifespan of 4-5 months. The
researchers first show that the zooidal epidermis is a major tissue affected by
the ageing process. Using in situ hybridisation, they also demonstrate that the
expression of mitochondrial respiratory chain (MRC) genes decreases in the
epidermis during ageing but is restored when budding commences –
mitochondrial deterioration is a hallmark of senescence. The polycomb group
gene Eed is similarly activated during budding and deactivated during ageing.
Finally, the researchers show that Eed is involved in MRC activation. These
results indicate that the senescence-related decline in the mitochondrial
gene activities of P. misakiensis reverses during budding, and implicate
polycomb group function in this
reprogramming of cellular senescence.
Jane Bradbury
DEVELOPMENT
STATus of cell competitors
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