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

28 NORMA L DEVELOPMENT
Chapters 2 and 11) . I n th e rodent , thi s occur s
during the secon d hal f of gestation (Angevin e
and Sidman , 1961 ; Lun d an d Mustari , 1977 ;
Gardette e t al, 1982; Miller, 1985) .
2. Postmitoti c neuron s prepar e t o migrate . The y
remain i n the proliferativ e zone s for up to 18 -
26 hours, th e amoun t o f time increasin g wit h
the age of the fetu s (Miller, 1999) . Durin g thi s
time youn g neuron s exten d thei r leadin g pro -
cesses whic h boas t pioneerin g filopodi a an d
laniellipodia that explor e th e environment an d
define th e directio n o f movemen t (Rakic ,
1972). They may move laterally within the proliferative
zones (Noctor e t al., 2004).
3. Th e neuron s actively move from th e prolifera -
tive zone s throug h th e intermediat e zon e
and ente r th e immatur e gra y matter. This ste p
involves th e choreographe d movemen t o f
the nucleus toward the leading process and th e
retraction o f th e trailin g proces s (Hatte n an d
Mason, 1990 ; Raki c et al, 1996) . Neuronal migration
i n th e neocorte x o f mic e an d rat s i s
completed b y the end of the first postnatal week
(Berry and Rogers , 1965 ; Miller, 1999) .
4. When a neuron reaches its final destination, its
nucleus cease s th e forwar d movement . A t
this site , th e neuro n differentiate s and elabo -
rates a characteristic morphology (Miller, 1981 ,
1986).
The migratio n o f neocortical neuron s can follow a
radial o r tangential pat h (Rakic , 1990; Miller , 1992 ;
Nadarajah an d Parnavelas , 2002) (Fig. 3-1) . Th e former
describes a process whereby neurons migrate in a
direction perpendicula r t o th e surfac e of the latera l
Protein and Function
Filamin A, actin binding protein
Doublecortin, microtubule-associated protei n
LISl/PAFAHIb, interacts with tubulin, dynein,
NUDEL, mNUDE
Reelin, ECM protei n
POMT1, presumed glycosyltransferas e
POMT2, presumed glycosyltransferase
POMGnTl, glycosyltransferase
Eukutin, presumed glycosyltransferase
Large, presumed glycosyltransferas e
FIGURE 3- 1 Multipl e migratio n route s o f cerebra l
cortical neurons . Cerebra l cortica l projectio n neu -
rons ar e generate d i n th e ventricula r zon e (VZ )
and subventricula r zon e (SZ ) o f the developin g ce -
rebral wall . Th e migratio n rout e o f thes e neuron s
is radia l (1) . Loca l circui t neuron s ar e generate d
in th e media l ganglioni c eminenc e (GE) . The y
undertake several migration routes (2 , 3, and 4) that
involve tangentia l migratio n an d radia l migration .
CP, cortical plate ; IZ, intermediate zone ; MZ, mar -
ginal zone .
ventricles (pathwa y 1) , wherea s th e latte r refer s t o
neurons as they migrate along a pathway that parallels
the surfac e o f th e latera l ventricl e (pathway s 2-4) .
This chapter review s the basic principles of radial and
tangential migration , molecula r event s underlyin g
normal neurona l migration , an d som e molecula r de -
fects tha t distur b neuronal migratio n to cause neuro -
logical disorders (Table 3-1) .
TABLE 3- 1 Genetic s of neuronal migration disorders in humans
Gene
FLNA
Dcx
PAFAHIB
Rein
POMT1
POMT2
POMGnTl
FCMD
Large
Structural Phenotype
Peri ventricular heterotopia
Double cortcortex syndrome s
Subcortical band heterotopi a
Type I lissencephaly
Lissencephaly
Walker- Warburg syndrome Polymicrogyria
Walker- Warburg syndrome Polymicrogyria
Muscle-eye-brain disease Polymicrogyria
Fukuyama congenital muscula r dystroph y
Polymicrogyria
MDC1D, Polymicrogyria