Brain Development
Neural Induction – The First Step Involved
in Forming Neural Tissue
One of the most important events that
occur during early vertebrate embryogen-
esis is
, by which all the three
germ layers;
ectoderm, mesoderm
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
The organizer tissue in their experiment
had the ability to pattern the mesoderm,
including the
(±ig. 1a). Similar
organizer regions have been shown to have
the axial mesoderm in various organisms,
and these regions indeed induce addi-
tional neural tissues/axes in developing
embryos. Collectively, such processes are
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
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
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