Healthcare and Medicine Reference
In-Depth Information
Crest cells
form ganglion
Glia cells
Nrg-1
Migrating
crest cells
Nrg-1
receptor
A
Differentiation
N
N
N
Neurons
Cultured crest cells
+Nrg-1 or Delta
-Nrg-1
or +BMP2
N
G
G
N
B
C
N
N
G
N
G
N
G
G
N
G
G
G
G
G
N
G
N
80% neurons
10% neurons
FIGURE 4.17 Specification of peripheral glia. A. Normally crest cells of the DRG produce neurons and
gia (see text) and if placed in culture, crest cells give rise to both neurons (N) and glia (G). B. Removal of
Nrg-1 or addition of BMP2 increase the number of neurons. C. Addition of the secreted signal Neuregulin to
the medium or expression of Delta enhances the proportions of glial cells developing from the culture.
migrate along radial glia to settle in one of six differ-
ent layers (Figure 4.18). In Chapter 3 we discussed the
mechanisms that control the migration of these cells
to their different layers; but what makes the cells of
each layer distinct? The cells in the different layers of
the cortex have layer-specific projection patterns.
Thus, in the visual cortex, Layers 2 and 3 neurons are
pyramidal cells that project to other cortical areas;
Layer 4 cells are small stellate local interneurons that
receive input from the thalamus; and Layers 5 and 6
cells are the largest pyramidal neurons and project to
other parts of the brain, and even the spinal cord. How
do the cells of a particular layer acquire their specific
identities, such that they project to the appropriate
targets?
Studies by McConnell and her colleagues have
asked whether the progenitors of the cells destined for
the deeper layers are somehow intrinsically different
from progenitors of the cells destined for the upper
layers, using cell transplantation in ferrets. In the
ferret, Layer 6 cells are born in utero at embryonic day
29 (E29). Weeks later, cells born at P1 just after birth,
are fated for Layers 2 and 3, and must migrate through
Layers 6, 5, and 4 which have already formed. To test
the idea that cells acquire laminar fate soon after they
are born and before they migrate, cells generated in the
ventricular zone of E29 ferrets were transplanted into
older P1 hosts (Figure 4.19). Although their time of
birth would have fated them for a deep layer, the
experiments showed that many of the transplanted
cells switched their fates and ended up in Layers 2 and
3, suggesting that these young cortical neurons are
flexible with regard to fate (McConnell, 1988). Further
studies showed that cell interactions are involved in
this commitment since if the E29 cells are removed and
cultured with other E29 cells for a number of hours,
their deep layer fate is fixed even when challenged by
transplantation to an older environment (McConnell,
1995). What about the reciprocal experiment, the trans-
plantation of P1 precursors into E29 hosts? When P1
precursor cells were transplanted into younger brains,
these cells all differentiated into Layer 2 and 3 cells,
even though the host neurons around them were dif-
ferentiating as Layer 6 neurons. Thus, these P1 cells
seemed to have lost the competence to differentiate as
deep layer cells (Figure 4.19).
This loss of competence appears to be a sequential
process, as illustrated by the transplantation of pro-
genitors in the middle stages of cortical development.
When the progenitors of Layer 4 neurons born at E36
are transplanted into older P1 brains, in which Layers
2 and 3 were being generated, they also generate Layer
2 and 3 neurons. However, when E36 progenitors are
transplanted into a younger E29 hosts, they show a
restricted potential ending up in Layers 4 and some-
times 5, but not Layer 6 (Desai and McConnell, 2000)
(Figure 4.19). These results suggest that environmen-
tal cues can influence precursors to produce neurons
of different cell types, but that the competence of these
precursors becomes increasingly restricted over time.
Thus, they can respond to an older environment but
not a younger one.
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