Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1200 Chapter 21: Development of Multicellular Organisms
roof plate and
adjacent cells
secrete BMP and
Wnt proteins
neural
tube
floor plate and notochord
secrete Sonic hedgehog
protein
(A)
motor
neurons
(B)
developing
spinal cord
sensory
neurons
lumen of
neural tube
(ventricle)
DORSAL
roof plate
floor plate
VENTRAL
dividing
neural
progenitor
cells
mantle
zone
groups of
differentiating
neurons
Figure 21–69 A schematic cross section
of the spinal cord of a chick embryo,
showing how cells at different levels
along the dorsoventral axis acquire
different characters. (A) Signals that direct
the dorsoventral pattern. Sonic hedgehog
protein from the notochord and the floor
plate (the ventral midline of the neural
tube) and BMP and Wnt proteins from
the roof plate (the dorsal midline) act as
morphogens to control gene expression.
(B) The resulting patterns of cell fates
in the developing spinal cord. Different
groups of proliferating neural progenitor
cells (in the ventricular zone, close to
the lumen of the neural tube) and of
differentiating neurons (in the mantle zone,
further out) express different combinations
of transcription regulators. Neurons
expressing different transcription regulators
will form connections with different partners
and may make different combinations
of neurotransmitters and receptors.
Colors represent different cell types and
combinations of regulatory proteins.
Extracellular morphogen gradients, however, are not the only way to generate
cell diversity. As we saw earlier in our discussion of Drosophila neuroblasts (see
Figure 21–36), different cell types can also be generated by temporal patterning,
in which an intracellular program changes the character of a progenitor cell over
time, giving rise to different cell types as development progresses. This mechanism
also seems to operate in vertebrate neurogenesis. The most striking illustration
comes from study of another part of the CNS—the mammalian cerebral
MBoC6 m22.80/22.69
cortex.
Although the cerebral cortex is the most complex structure in the human
body, it has a simple beginning—from the anterior neural tube. As in the spinal
cord, the cells that form the walls of the tube proliferate, and the neuroepithelium
thickens and expands as they divide. On a predictable schedule, the divisions
of the neuroepithelial cells begin to produce a succession of cells committed to
terminal differentiation as neurons. These future neurons are born close to the
lumen (the central cavity) of the tube. From here, they migrate outward, losing
attachment to the lumenal surface and crawling outward along neighboring cells
that continue to span the full thickness of the neuroepithelium. These latter neuroepithelial
cells do double duty, functioning as progenitors of neurons and glia,
and as supporters of the epithelial architecture. They become stretched out as
radial glial cells, forming a scaffold that continues to span the neuroepithelium
even as this grows to an enormous thickness (Figure 21–70). At the same time,
the radial glial cells continue to divide as neural precursors, giving rise to both
neurons and glial cells—new radial glial cells as well as glial cells of other types.
The newborn neurons, migrating along the radial glial cells, find their appropriate
resting places in the developing cortex, where they mature, and from these sites
they send out their axons and dendrites. The first-born neurons settle closest to
their birthplace near the lumen, while neurons born later crawl past them to settle
farther out (Figure 21–71). The successive generations of neurons thus build
up as a series of cortical layers, ordered by birthdate and endowed with different
intrinsic characters.
Strikingly, single cortical progenitor cells isolated in culture generate distinct
types of cortical neurons and glial cells, with the timing and characteristics appropriate
to specific cortical layers. These observations suggest that the neural progenitors
in the developing mammalian cortex, much like the Drosophila neuroblasts,
step through an intracellular developmental program that generates the
ordered succession of different nerve cell types.