zone）之神經幹細胞（radial glial cell）分裂生成新生的神經細胞，新生的神經細胞沿著radial
et al., 2005)。
et al., 2009)。在這個過程中的物理特性為何，中心粒、細胞核、細胞骨架相互間之交互作用等過程目前仍有許多值得探討的地方。
make use of a variety of mechanisms for directed migration.
Recent attention has been directed at the unusual migratory
behavior of a form of stem cell - the neural precursor.
These cells, located at the surface of the ventricles
in the developing brain, give rise to all neuronal and
glial cells in the developing brain. They undergo numerous
successive cycles of division to populate the forming
cerebral cortex, the part of the brain responsible for
cognitive function. As new cells are produced they migrate
outward over considerable distances to find their proper
location in the developing brain. Defects in the division
of these cells can lead to microencephaly, or "small
brain," and defects in migration can lead to a
number of brain developmental disorders e.g., lissencephaly
(smooth brain), double cortex, and periventricular heterotopia.
However, how neuronal migration affects brain development
and how defects in this process cause human developmental
diseases in newborn infants were largely unknown.
on their site of origin, neural precursors may pass
through a series of morphological stages, but in each
case long-distance migration involves a specific cell
form which exhibits behavior not seen in the migration
of non-neural cells. Existing evidence suggests that,
unlike most cell types, newborn neuron moves in a strikingly
discontinuous, or saltatory, manner. In these events,
subcellular structures such as the cytoskeleton ("bones"
of cells), the nucleus (which contains the genetic material,
DNA) and other organelles ("organs" of cells)
must move in a specific sequence. However, the molecular
mechanisms which these organelles utilize are still
unclear and the genes that are involved are largely
evidence has indicated that the lissencephaly gene LIS1
play an essential role in neuronal migration. Previously,
by live imaging of neural precursor cells in brain slices
Dr. Tsai has shown that deficiencies in the LIS1 gene
cause abnormalities in neuronal redistribution. These
results indicated that LIS1, and presumably its regulatory
target cytoplasmic dynein (a molecular motor protein),
were responsible for coupling cell body movement to
migration. The stage of migration in which LIS1 and
cytoplasmic dynein participate is uncertain.
studies aim to define the subcellular events involved
in neural precursor cell migration and to define the
roles of dynein and LIS1 in this process. In order to
elucidate the mechanism of neuronal migration and its
role in causing braining developmental diseases, we
used advanced molecular technologies to fluorescently
label the cytoskeleton, the nucleus and other organelles
in neuronal cells and monitored of the behavior of these
subcellular structures in migrating neurons across live
brain tissue. This research reveals a variety of novel
cell behaviors and provides the first-time demonstration
of the subcellular behavior of neural progenitors in
the live developing brain.
foundthat centrosomes often moved far in advance of
nuclei, which exhibited extreme saltatory behavior.
Inhibition of LIS1 and dynein blocked both centrosomal
and nuclear movement. To gain insight into the underlying
mechanisms for dynein-mediated movement, we made the
first use of live microtubule imaging in living brain
tissue, and observed a clear, centrosome-centered radial
arrangement which persists throughout the migration
cycle. In contrast to other undifferentiated cells,
the distribution of neural precursor microtubules is
markedly constrained by the narrow neural processes.
By immunocytochemistry, we found a pronounced accumulation
of dynein within the migratory process correlated with
the onset of centrosomal movement. All these results
have brought about a number of striking and unique features
to the underlying organization and migration of neural
progenitor cells, and led to a comprehensive model for
how microtubule, nucleus, and dynein behavior are coordinated
to affect the complex temporal and morphogenetic behavior
of these cells.
behavior of the centrosome (green) and the nucleus (magenta)
in a migrating neuron (blue) during brain development.