research highlights
How angioblasts form veins
and arteries
Blood vessels are formed from capillaries
sprouting from existing vessels or de novo. A
third way of forming new blood vessels is now
described in Science (Science 326, 294–298;2009). Stainier and colleagues show that inzebrafish embryos, the first artery (the dorsalaorta) and vein (the caudal vein) are derived
from the same precursor vessel. Imagingof embryos with GFP-labelled endothelial
cells revealed that angioblasts sprout ventrally from the precursor vessel, after which
sprouts are terminated and an unconnectedcaudal vein is formed. The dorsal aorta
is formed subsequent to dorsal sprouting
by classic vasculogenesis. Knockdown ofknown vascular sprouting regulators of vascular sprouting, such as vascular endothelial
growth factor (Vegfa) and Notch, revealed
that Vegf restrains ventral sprouting throughNotch signalling, while promoting dorsalsprouting. Ephrins are tethered to the plasma
membrane and possess reverse signalling
properties, mediating bidirectional signalling in various developmental contexts. Here,the authors demonstrate that the sorting ofangioblasts towards ventral or dorsal migration is achieved through Ephrin signalling;
Ephrin B2a is induced by Vegfa in arterialfated angioblasts and limits their ventralmigration, while its ligand, Ephrin B4a,
promotes ventral migration of venous-fatedangioblasts. These experiments elegantly
demonstrate how angioblasts are directed

towards different fates, and are likely to berelevant for vascular development in othersystems. CKR

Traffic jam in the piRNA
world
Germline-specific PIWI-interacting RNAs
(piRNAs) are produced either through a
primary pathway, which loads them onto
the argonaute protein Piwi, or through anamplification loop, which involves additional activities of the Piwi-related proteins
Aubergine and AGO3. Whereas the amplification loop is fairly well understood, farless is known about the primary productionof piRNAs. Siomi and colleagues uncover a
new locus, traffic jam (TJ), which produces
piRNA in the somatic lineage of gonads
through this primary route (Nature, doi:10.1038/nature08501). The authors derived
an ovarian somatic cell line (OSC) fromDrosophila that expressed Piwi, but neitherAubergine nor AGO3. They found that in
OSC cells, Piwi associated with piRNAs thatwere mostly antisense to retrotransposons.
Several piRNAs in OSC cells do not exhibit
the characteristics of amplification loop
products shown by those derived from theknown flamenco piRNA locus and 3′UTRof the gene encoding the transcription factor TJ. Somatic cells mutant for TJ or Piwi
fail to envelop germline stem cells, and theadhesion molecule Fasciclin III, known to

Synaptic development: autophagy weighs in
During autophagy, cellular components are sequestered in autophagosomes that deliver
them to the lysosome for degradation. Shen and Ganetzky describe a new role for autophagy
in regulating synapse development in the fruit fly (J.Cell Biol. 187, 71–79; 2009).
The authors found that mutations in genes that function at various points along theautophagy pathway result in reduced neuromuscular junction (NMJ) size. Inducing
high levels of autophagy leads to NMJ overgrowth, similar to that observed in highwire(hiw) mutants, which encode a defective ubiquitin E3 ligase. As in hiw mutants, NMJ
overgrowth induced by autophagy was suppressed by mutations in wallenda, a MAPK
kinase kinase, or a dominant-negative form of the c‑Jun N‑terminal kinase (JNK) bsk.
Moreover, Hiw overexpression suppressed the effects of autophagy on NMJ overgrowthand, conversely, reducing Hiw levels enhanced NMJ overgrowth. Hiw levels were higher
in autophagy pathway mutants, suggesting that autophagy controls NMJ development
by downregulating Hiw levels. hiw is epistatic to atg mutants and increasing Hiw levels
resulted in NMJ undergrowth, suggesting that Hiw is a key effector of NMJ development,
downstream of autophagy.
Whether autophagy targets Hiw directly and the details of how autophagy results in specificdegradation of Hiw remain to be determined. SS

be involved in this process, is upregulated
in these cells. Piwi is absent from TJ-mutant
gonadal somatic cells and TJ can bind thePiwi promoter. Thus TJ regulates primarypiRNA production in the somatic lineage byacting on Piwi, possibly at the transcriptional
level, and by providing a source of piRNAs. Inturn, the Piwi pathway can regulate gonadalfeatures, perhaps through piRNA-mediatedcontrol of adhesion molecules.
NLB

The importance of being
asymmetric
Stem cells (SCs) self-renew and generate differentiating progenitors through asymmetriccell division. Progenitors proliferate actively,
whereas undifferentiated SCs remain mostlyquiescent, except for undergoing transient
bursts of symmetric division whenever theSC pool needs to expand, as during development or following tissue injuries. Do cancer
SCs behave differently?
Using an ErbB2 transgenic model ofbreast cancer and tumour-derived mammospheres, Pelicci and colleagues (Cell 138,1083–1095; 2009) show that, compared with
their normal counterparts, tumour mammary SCs exhibit a higher frequency of symmetric divisions and increased self-renewal,
higher replicative potential and the ability
to grow indefinitely. Interestingly, mammary SCs isolated from p53-null mice also
showed increased symmetric divisions andhigher replicative potential both in vitro andin vivo; indeed, p53 stability was reduced in
Erb2B tumour samples. Stabilization of p53
with Nutlin3, a small molecule that inhibits
p53 degradation, correlated with the restoration of asymmetric divisions in cancer SCs
and a reduction in tumour growth. Thus, one
mechanism of tumour suppression by p53
might involve maintenance of tissue homeostasis through regulation of SC division
polarity. While further studies will elucidate
how p53 inactivation leads to increased symmetric divisions, these findings support thehypothesis that polarity loss may contributecausally to cancer. SG

By Nathalie Le Bot, Silvia Grisendi,Christina Karlsson
Rosenthal & Sowmya Swaminathan

nature cell biology volume 11 | number 11 | NOVEMBER 2009 © 2009 Macmillan Publishers Limited. All rights reserved.

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