Brain Development: Normal Processes and the Effects of Alcohol ...

52 NORMA L DEVELOPMENT
FIGURE 4- 4 Midlin e guidance . Schemati c diagram s o f developin g mam -
malian spinal cord depict the trajectories of eommissurally projecting neurons
relative to the roo f plate an d floor plate in cross-section (A) or molecular gradients
i n longitudinal preparation through th e ventra l rnidline (B). Pre-crossing
axons are repelled fro m dorsa l midline by BMP? in the roo f plate (no t shown)
and attracte d ventrally by netrin an d Sh h gradient s emanatin g from th e floor
plate (shade d circles). Post-crossing axons become sensitive to Slit - and Sema -
phorin 3 B an d F-mediate d repulsio n an d d o no t retur n t o th e floo r plate .
(Source: Modifie d from Williams et al, 2004)
animals, Rig- 1 concentration s decreas e an d Robo- 1
and - 2 amounts increas e soo n afte r crossing , whic h
may serve to expe l axon s from th e midlin e (Sabatie r
et al. , 2004) . Thi s expulsio n i s probabl y aide d b y
Robo-Ts abilit y t o silenc e DCC-mediate d attractio n
to netrin by binding directly to DCC i n the presenc e
of Slit (Stein an d Tessier-Lavigne , 2001 ) or by growth
cone desensitizatio n t o th e hig h concentration s o f
netrin at the midline (Piper et al., 2005). Sema-3B, an
additional solubl e repellan t secrete d b y th e floo r
plate, prevent s axon s from returnin g t o th e midlin e
via interactions with its receptor neuropilin- 2 (Zou et
al., 2000) . Afte r crossing , th e positio n o f longitudi -
nally runnin g tract s appear s t o b e regulate d b y th e
midline Sli t gradien t interactin g wit h Robo- 1 o r -2
(Rajagopalan et al. , 2000 ; Simpso n et al. , 2000) .
Concurrently, Wnt-4 , actin g throug h it s recepto r
frizzled3, an d Shh , actin g throug h hedgeho g inter -
acting protein , hel p orien t axon s anteriorl y i n th e
longitudinal axi s (Lyuksyutova et al., 2003; Bourikas
er al., 2005) , but the interactio n betwee n thes e cue s
has ye t t o b e investigated . Collectively , thes e dat a
support th e idea s tha t certai n guidanc e cue s ca n
trump th e other s an d sugges t that cues are processe d
hierarchically rather than being integrated.
Generating Retinotectal Maps
Once axon s reach thei r target region, they terminat e
in highly organized pattern s that reflect their points of
origin. Th e projection s extending fro m retina l gan -
glion cell s t o the tectu m i n fish and frog s an d t o th e
superior colliculus in rodents has served as the canon -
ical syste m fo r studying the developmen t o f pattern -
ing. I n mos t mammals , a ligh t shown i n th e fa r lef t
visual field projects on the ventronasal part of the lef t
retina, whic h i n tur n project s contralaterall y t o th e
caudomedial regio n o f the superio r colliculu s (Fig .
4-5). I f a n experimente r systematicall y move s a
recording electrode rostrall y through th e superior colliculus,
th e stimulatin g ligh t sourc e need s t o b e
moved i n a n orderl y progression fro m lef t t o righ t to
activate th e neurons . Thus , th e superio r colliculu s
contains topographic map s of the visual field.
A larg e bod y o f dat a suppor t th e correlatio n o f
ephrin gradient s i n the retin a an d superior colliculus