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

62 NORMA L DEVELOPMENT
regulated (Bevan s et al, 1998 ; Suchyn a e t al, 1999 ;
Bukauskas an d Verselis , 2004) . Thi s spatiotempora l
control o f ga p junctio n gatin g an d permeabilit y i s
likely to have consequences fo r nervous system assembly;
however , the effec t o f connexin or gap junction
deficiencies on synapse formation, targeting, or stability
have yet to be examined.
The mechanism s guiding spatial targeting of connexins
or cell type-coupling specificity in the nervous
system als o hav e ye t t o b e examined . Wor k i n non -
neural tissues , however, suggests that molecules typi -
cally associated with other types of junctions facilitate
connexin targeting to sites in the plasm a membrane .
For example , E-cadheri n overexpressio n ca n pro -
mote normal concentrations o f connexin targetin g to
the plasma membrane in skin papilloma cells and alter
couplin g preference s i n transfecte d melanoma s
(Prowse e t al. , 1997 ; Hs u e t al, 2000 ; Hernandez -
Blazquez et al., 2001). Additionally, normal gap junction
formatio n betwee n len s cell s i s disturbe d i n
Nr-CAM-deficient mice an d b y antibodie s agains t
N-cadherin (Frenzel and Johnson, 1996 ; Lustig et al.,
2001). The tigh t junctio n components zonula occludens
1 an d som e claudin s als o associat e wit h ga p
junctions with as yet undetermined functional conse -
quences (Duffy e t al, 2002).
CONCLUSIONS
Neuroscientists hav e define d a serie s o f significant
events o r stage s essentia l fo r norma l differentiatio n
and integratio n of neurons into a functional network.
Recent work links particular stages of differentiation
with the function of particular molecules o r molecular
families, and this work has provided the necessar y
tools wit h whic h mechanism s ca n b e pursued . On e
challenge fo r futur e experimenter s i s t o determin e
how molecula r pathways of apparent overlappin g or
converging functio n ar e parse d int o specifi c an d
meaningful outcomes .
Abbreviations
AMPAR ot-amino-3-hydroxy-5-methyl-4 -
isoxazole propionate recepto r
BDNF brain-derive d neurotrophic facto r
BMP bon e morphogenic protein
CAM cel l adhesion molecul e
cAMP cycli c adenosine monophosphat e
cGMP cycli c guanosine monophosphate
CNS centra l nervou s system
CRMP collapsi n response mediator protei n
DCC delete d in colorectal cancer
ECM extracellula r matrix
EM electro n microscopy
GABA y-aminobutyri c acid
GDF growt h differentiation factor
MAP microtubule-associate d protein
MNTB media l nucleus of the trapezoid body
Ng-CAM neuron—gli a cell adhesion molecule
NMDAR N-methyl-D-aspartat e recepto r
NMJ neuromuscula r junction
Nr-CAM NgCAM-relate d cell adhesion molecule
OD ocula r dominanc e
PSD postsynapti c density
PTV Piccolo-Bassoo n transport vesicle
Shh soni c hedgehog
S mo smoot h ened
SNARES solubl e n-ethylmaleimide-sensitiv e
fusion protein-attachmen t protei n
receptors
SNAP-25 synaptosom e associated protein-25
SV synapti c vesicle
SynCAM synapti c cell adhesion molecul e
ACKNOWLEDGMENTS Th e author s than k loan a
Carcea, Elizabet h Kichula , and Cynthi a Kwong for their
careful readin g and critica l comments on this chapter and
Alice Elste for her image of a chemical synapse. The au -
thors are supported by the Nationa l Institute s of Health
(CDM, IHB , an d DLB) , Societ y fo r Neuroscienc e
(TRA), and an Irma T. Hirschl Award (DLB).
Equal contribution s for th e writin g o f thi s chapte r
from Mint z (polarity and motility) , Bekiro v (guidance),
and Anderson (synaptogenesis).
Notes
1. "Dale' s principle/ ' base d o n argument s that transmitter
function o f a neuron is distinctive an d "un -
changeable" (Dale, 1935), actually was first defined
by Eccles (1957 ) t o state "that the sam e chemical
transmitter is released from all the synaptic terminals