Brain Development
89
1
Neural Induction – The First Step Involved
in Forming Neural Tissue
One of the most important events that
occur during early vertebrate embryogen-
esis is
gastrulation
, by which all the three
germ layers;
ectoderm, mesoderm
,and
endo-
derm
are Frst established. Neural tissue is
formed in the ectodermal layer overlying
the mesodermal tissue. In 1924, Spemann
and Mangold demonstrated that during
early gastrulation a distinct population of
cells around the dorsal lip in amphibian
embryos had the ability to induce an ad-
ditional head and trunk if grafted into the
opposite site of the dorsal lip (i.e. presump-
tive epidermis) of a host embryo (±ig. 1a).
Notable was the fact that the cells in the
newly formed head and/or trunk struc-
tures were totally derived from the host
embryo, indicating that the grafted tissue
had an instructive role in organizing the
head and trunk tissues. The cells that har-
bored the ability to induce the secondary
axis in the embryo were named
organizer
.
The organizer tissue in their experiment
had the ability to pattern the mesoderm,
including the
notochord
(±ig. 1a). Similar
organizer regions have been shown to have
aro
leintheforma
t
ionandpa
t
tern
ingo
f
the axial mesoderm in various organisms,
and these regions indeed induce addi-
tional neural tissues/axes in developing
embryos. Collectively, such processes are
termed
neural induction
. While Spemann
and colleagues proposed that distinct tis-
sues appear to induce either anterior or
posterior characters in the neural tissue
of amphibian embryos, Nieuwkoop later
suggested a two-step model. In this case,
an early activating signal induces neu-
ral tissue with an anterior character (i.e.
forebrain), and a second posteriorizing or
transforming signal that converts neural
tissues into a more posterior character fur-
ther produces regional differences along
the axis (i.e. hindbrain and spinal cord).
Both classical models that explain frog
neural induction involve a degree of neu-
ral patterning as very early events. In
mice, three distinct tissues, the early gas-
trula organizer (EGO), anterior visceral
endoderm (AVE), and anterior epiblasts,
have been implicated in playing a critical
role in the induction of anterior neural
structures during early gastrulation stages
(±ig. 1c). EGO is a cell population in the
early primitive-streak stage of the embryo,
which displays the cellular properties typ-
ical of Spemann’s frog organizer. The
transplanted EGO/node region indeed has
the ability to induce the secondary axis with
posterior neural characters, but the AVE as
well as the anterior epiblast are further re-
quired to induce complete sets of anterior
neural structures in mouse embryos, indi-
cating that multiple signaling mechanisms
should be involved in neural induction
events to simultaneously generate regional
differences along the Anterior–Posterior
(A–P
)ax
is
.Iw
i
l
lcomebacktoth
ispo
in
t
later (Sect. 2,on A–P patterning).
Basic molecular mechanisms involved
in neural induction appear to be conserved
among vertebrates and invertebrates, al-
though tissue organization of the three
germ layers varies from species to species.
Key molecules determining neural and
nonneural tissues are a signaling fac-
tor, Decapentaplegic (Dpp)/bone morpho-
genetic protein (BMP), and its antagonist
secreted from the axial mesoderm, Shorted
gastrulation (Sog)/Chordin. BMP signal-
ing participates in the process that converts
cells into surface ectoderm (skin), and cells
in which the Dpp/BMP signal is antago-
nized by Sog/Chordin inhibitors are fated
to form neural tissue (±ig. 1a). It is now
known, however, that vertebrate neural
