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

46 NORMA L DEVELOPMENT
FIGURE 4-1 Stage s of neurite development Th e Stag e 1 neuron lacks neurites
entirely. In Stag e 2 , immature neurites emerg e tha t are capable o f becomin g
either axon s or dendrites. When on e o f the immatur e neurites outgrows the
others i t becomes th e axo n and th e neuro n reache s Stag e 3 . The remainin g
immature processe s becom e dendrite s an d elaborat e an d branc h i n Stag e 4 .
Synaptogenesis and spinogensi s occur i n Stag e 5 , which i s not show n in this
diagram.
proven definitively , it i s generally believe d tha t th e
stages o f neurit e developmen t observe d i n cultur e
also occu r i n situ . Nearly all data tha t addres s ques -
tions about neuronal polarity are derived from experiments
i n whic h neuron s ar e grow n i n dissociate d
cultures where individual processes can be identified
and followed over time.
Polarization is Initiated b y
Axon Specificatio n
All early neurites o n a particular neuro n ar e capabl e
of becoming axon s or dendrites . On e ultimatel y acquires
axona l characteristic s an d th e remainde r as -
sume a dendriti c fate . I n a Stag e 2 neuron , eac h
process undergoe s cycle s o f extension an d retractio n
until on e neurit e outgrow s th e other s b y a critica l
length—lOjLim i n hippocampa l neurons—an d be -
comes th e axo n (Gosli n an d Banker , 1989) . I f a
recently formed axo n is transected to a length compa -
rable to that of the other neurites, one of the other minor
processe s typicall y becomes th e axo n an d th e
stump of the original axon adopts dendritic character -
istics (Dott i an d Banker , 1987) . Thus , ever y Stag e
2 proces s ha s the potentia l t o become the axon , bu t
the presenc e o f a specifie d axo n actively promotes a
dendritic fat e for the remainin g neurites . This mode l
is supporte d b y data showin g that dendriti c matura -
tion ca n occu r onl y after axo n specification (Cacere s
et al, 1991) .
As one neurit e outgrows the other s by virtue of interactions
wit h loca l environmenta l factors , i t give s
rise t o a positiv e feedback loo p tha t create s tw o dis -
tinct compartments (Crai g and Banker , 1994) . As development
continues , som e protein s an d organelle s
become segregate d int o on e o f th e tw o compart -
ments, an d th e differen t complement s o f proteins in
mature axon s an d dendrite s underli e th e functiona l
and morphologica l differences betwee n the two types
of neurites . I n recen t years, some progres s ha s bee n
made in elucidating the molecular basis of axon specification
an d subsequen t maturatio n events , bu t a
complete mode l ha s not yet been formulated.
Role of the Cytoskeleton in
the Establishment of Polarity
A considerabl e bod y o f evidenc e support s th e hy -
pothesis that microtubules are involved in axon specification.
Quantitativ e analyse s o f seria l electro n
microscopy (EM ) reconstruction s o f minor processe s
and axon s in Stag e 2 and Stag e 3 neurons revea l tha t