The structure and function of serpins

This Way Up, This End First:
The molecular basis of
axis formation in
Drosophila
MOSI orgmismr haw O &&y dirlinguithoblc hcod ond lai!,
~ ~ . ~ ~ ~ ~ ~ p h l r
fiont ond bob There oxet OIC citobiirhed early in embyonic
dcvciopmcnf hlil Tor most onimdr oimoil nothing it known
obovt the prc& mrchaoirmi invdvrd In the fmiffly,
Oiorqhh mymmety is codified in the developing egg, md
~ rcreorch ~ in Umbridgcir beginning to unrorcr~hcmoieculai
~ r ~ ~ p i U i r n n n . . f i h ~ ~ ~ ~ mechinisms ~ ~ , ~ bywhih ~ ~ i there , ~ me$ f ~ ors ~ tprcifed. * ~ ~ ~ i .
Theawad ofthe 1995 NobeIPtize for Phyiologyor Medrine
to Ed Lewir. Chtirliane Ntirdein4oihsd and Eti~ Wielchhaur
was recogn'~n ortheirpimemg or gmtis 10 a~tpe
eady development in Drnrophiio. But it also reIleued the piuoial
mie the fmMy has come 10 plsy in developmental biology.
HOW a fly is pui t~gether ii now undentood in iema?eble
detail. and many ofthe ptincipier discovered in OrniophiIo have
twned out to be widely appitable 10 other organism$.
One area of early development under cloie rcnniny ir the
mshanirm by which body axer are enab1,rhed nier are highly
arymmettical - heads facing fowads, wings on the back iegr
on the underride. and IO OR Inteming~. both head4a.tail
(antem.portetiot) and fmnt-to.batk (dom-mntial) poiltitiel
are already established in the unfeniïmed egg Atthe Wellcome
TdCancer Research Campaign Innilute for Cancer and
Deveiopmental Biology in Cambtidge. Dr Daniel 51 lohnrton
and cdieaguer are beginning 10 cianiy the moierdar mcchanimi
by which there asymmettiEI are mated.
I2
DROSOPHILA
A fmrhiy laid Drnrophiio egg il mvghly oval in shape and look
almort iymmem~al. in facc the inride of the egg is highly polar.
ized. owing to the localized dimbution of merrenger RNA$
encoding key pmteinr: bmd mRNA is localized to the anterior
and orbr mRNA $0 !he ponetior. In nom1 Ilia. biraid deliner
where the head will form and etkordicttatcr where the
abdomen will devebp.
How is this aiymmefry mated1 Eggs begin life in a ~flllmre
lvl~wn II the egg chamber. which is bmed when a Rem tell
divides four times 10 give a cyst of 16 ceilr: onne ofthere cells
develops into the wcyte - which will wmtually be the egg -
while the other 15 become 'nune celis', imerconnmed LeIli
fhl rvpply the ooqe With the matetialr 11 needs to gmw and
deveiop.Artheoo~ytegmwr.theegg chambertaker m a dirtincm
shape. with the ooqe iseifat the ponetior. the rime
celis atthe antetioranda tingl~.~diI~y~rofq~hhelium-f~llide
ceils - rumunding all I6 gemline celii. How the ooqe
ilimei to o~ccupy the ponm.oiend ofthe egg rhamberir not
dear. bu1 this positioning if eimtial to the ertabiithment of
both the antao.porletioi and dom-venml =CI.
WO* fmm Cr 51 Johnswn's and other labs ha revealed that
the key tD axis fomtion is a setier of signals relayed between
the developing oocyte and iumunding follide cell$. tek to
their own dwicer. ioliicie ceils I the portetior ofthe egg
rhamberaregeneti~aUypmgrammed to adopt an sntetiorfate.
A$ it develops. the Gcyte rends a signai to these follicle tells,
which stops them following the default anietioi pathway and
'
imtcad Commis them to a posterior fare.
Later. the ponetior foiiide ceils signal back 10 the oocyte The
eNea ofthi5 signal is 10 reorganize the intemal scaffolding or
~ y t ~ ~ ~ eooqe, i ~ IpeLiliaiiy t ~ ~ itr miuDtubu~e " krk
Unlike Icaliddmg. mimubules are directional: the labels 'pius'
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