Brain Development
109
4
Molecular Aspects of Generating Distinct
Types of Cells and/or Cellular Organization
(e.g. Nuclei, Layers, and so on) in Patterned
Tissue
4.1
Generation of Neurons
There are mainly two molecular mech-
anisms in generating a variety of neu-
rons. One is the cell intrinsic mechanism
(cell autonomous) and the other is the
cell nonautonomous mechanism. These
two mechanisms might closely corre-
late with each other. In the vertebrate
nervous system, the latter mechanism
plays major roles, yet the former mech-
anism is indispensable. In Sects. 4.1.1
and 4.1.2, I summarize those molecular
mechanisms involved in the production
of multiple cell types in the nervous
system.
4.1.1
Cell Intrinsic Mechanisms
Cell intrinsic mechanisms play impor-
tant roles especially in animals where cell
lineage is strictly regulated during devel-
opment. Cell intrinsic differences could
be mainly realized by asymmetric cell
divisions in which particular sets of de-
terminants might be differentially divided
into two daughter cells. For example, in the
process of
Drosophila
neurogenesis,
pros-
pero
mRNAsaswellastheproteinproducts
are distributed asymmetrically in the pro-
genitor cells (Fig. 9a). This asymmetric
distribution of Prospero is crucial in pro-
ducing distinct sets of neurons, because
prospero
encodes a transcription factor
and the molecule is transported into the
nucleus after asymmetric cell division, al-
lowing distinct sets of genes to be switched
on/off in each daughter cell (Fig. 9a). In
order to localize
prospero
mRNAs as well
as proteins asymmetrically in the progeni-
tor cell, the RNA-binding protein, Staufen,
and a Staufen binding protein, Miranda,
which can also bind to the Prospero pro-
tein, appear to play a central role and
Inscutable regulates the polarization of
these proteins (Fig. 9a). Inscutable protein
can also control the spindle orientation
in the cell, suggesting that this protein
is a main determinant of cell intrinsic
differences between apical and basal com-
partments in a cell. Curiously, Inscutable
can further interact with the Bazooka pro-
tein, another important determinant of
apical–basal polarity formation in a cell.
Bazooka homologs have been identi±ed in
the nematode
Caenorhabditis elegans
(Par-
3) as well as in vertebrates (ASIP; atypical
PKC isotype speci±c interacting protein),
indicating a conserved mechanism for
intracellular asymmetry beyond species.
Notable is the fact that the
Drosophila
glial/neuronal lineage can also be initi-
ated by the asymmetric distribution of
glial
cell missing
(
gcm
)mRNA(F
ig
.9a)
.As
gcm
encodes a transcription factor required for
glial fates, the asymmetric segregation be-
tween the two daughter cells may play an
essential role in the bifurcation of glioblast
and neuroblast lineages (Fig. 9a).
4.1.2
Cell Nonautonomous Mechanisms
It would be very important to control the
relative ratio of various cell types during
neural development. In this critical pro-
cess, Notch/Delta mediated cell–cell com-
munications (cell nonautonomous ma-
chinery) appear to play a pivotal role. The
Notch/Delta signaling pathway was ±rst re-
ported to be essential for the neurogenesis
of the
Drosophila
embryo, where cells that
happen to express a higher amount of lig-
ands, Delta, inhibit lateral cells expressing
receptors, Notch, to further differentiate
into neurons. This process is speci±cally
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