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Sr"rpperr{img Xissu*s


Vestibular lamina

Dental lamina

Tooth bud


Dentai larnina

Tooth bud

Developing mandibular

Fig*r*:.i-1* Bud

stage of

tooth devel*pnrerrt sren in coronal secii$n tA) and sagiltal section (B).

functinn. The supporring ectornesenchtmal celis


pack*d closely henearh and irrr:und the epirlreiial hud.


mi:rphologic diffcrences befi,r,e*n togth germs thirt give

rise ro ilifferent types of rr:etl-r. tr{ss-l is expressed u'ith
Srnp-4 in t1-re ruesench-vmal cells thiit ccudeuse arout:d
torrth huds,*i* embr,vc:s have ttr,:th develo;:ment
;:rrested at the hud stage, and Brnp-4 expression is lost
lrorn the mesenciryme r ruggesting rl-rar h{.is-l is required
for Bnrp-4 expressir:tr. I3rnp"4 is thlt ro rnaintain M.u-J
expres.siern in rvild-trye t*oth bud rnesenchyn:e , indicating th;rt Brnp-4 induces its ,.r*'tt cr1:rcssiorr via fuJ-qx-J.
Tor:th c{er,elopfi}errr can hc rescued in blsx- j i rrlhryos
by adt{ition i:f r:xugen.rur. Bh,'tP-4.

th* i:uil

mescachym.e is rccluireil
ttr rnainririn BnrJ:-? anrt Shh explessicrn ir-l the r:pitheliirrn.
Lr.rss *1'- Iirrp-4 expression in trfs::-i rnutants is acconrpn*
nied hy lass o{ Sllh exl.ressi,rn rt E12.5, rvhich c*n he

restored b,v *x*genr:us llltlP,4. Bltrcking SHH funcrion

witir neutrirliring ar:tilxrdies alsr: resrrits in loss r:f Brxp-l


The tran$ition irom burl t,-t cap marks the onset

Bmp-4 expresser{ in

cxprrersion. suggest.irrg Slrh and iimp-J ma,v be itr tl're sat're

pathwa), and that d*'"vn-regul*tion oi: fiilp-J in Mss" j
mutants nray be d.lurnrtream r:i rl-re l,:ss af SH]-l.
The [c'ss of -C] iH rignaling ot diflcrent stagtrs ol:torth

deveiopmenr has i.lentiiicd distinct tiine-dr:pendenr

requirements for SHll. Blocking S}{}{ sigr:aling usinr
rreutraliiing arltihoilies or fr',rskolin shorvs that at
811'El i SllH is reqr-rirecl for dental cpirheliLrm proliier-

atil]il ro lor*r rooth buds, *,hereas Llo'"'.king at Ei-) aflecrc

roorh hud rnorlrlrnlogy', l:ur l-.ul{s stili can lorm
r-eerh. Ceneric clisrupriorr ul Slir sigr:aiing flron"r EI2.5
hy ilrc-urecliated excisir:n r:f mrgeted Shh mrli ;rlleles