|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 20 October 2004
doi: 10.1242/dev.01436
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan
2 Department of Anatomy, Jichi Medical School, Tochigi 329-0498, Japan
3 Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
4 National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK
Author for correspondence (e-mail:
rkageyam{at}virus.kyoto-u.ac.jp)
Accepted 9 September 2004
 |
SUMMARY |
|---|
 TOP SUMMARY IntroductionMaterials and methodsResultsDiscussionREFERENCES |
|---|
Key words: Adherens junction, Basal lamina, bHLH, Neuroepithelium, Radial glia, Tight junction
|
Introduction |
|---|
|
TOPSUMMARYIntroductionMaterials and methodsResultsDiscussionREFERENCES |
|---|
; McConnell,
1995; Temple,
2001). During neurogenesis, radial glial cells are known to
undergo an asymmetric cell division, by which each radial glial cell forms one
neuron and one radial glial cell.
The size and shape of the nervous system largely depend on how many times
neural stem cells re-enter the cell cycle
(Ohnuma and Harris, 2003). For
example, the brain becomes enlarged when cell differentiation is delayed by
null mutation for the cyclin-dependent kinase (CDK) inhibitor p27Kip1, which
inhibits cell cycle progression (Fero et
al., 1996; Nakayama et al.,
1996), or by misexpression of a stabilized ß-catenin, an
effector for Wnt signalling, which induces cell proliferation
(Chenn and Walsh, 2002). The
timing of cell differentiation may also influence cell fate choice, because
neural stem cells change their competency over time during development
(McConnell, 1995;
Qian et al., 2000;
Temple, 2001). However,
although delayed cell differentiation by misexpression of a stabilized
ß-catenin increases neurons as well as neural stem cells, the enlarged
brain with massive expansion of the cortex has a normal spatial pattern of
neuronal differentiation (Chenn and Walsh,
2002). Thus, it is still obscure how the timing of cell
differentiation influences cell fate choice and the histogenesis of the
nervous system. Conversely, acceleration of cell differentiation was also
attempted by disrupting cyclin D and cyclin E genes, which are believed to
play an essential role in cell cycle progression
(Sherr and Roberts, 1999).
However, unexpectedly the defects of these cyclin-null mice are mild and occur
only at late stages (Fantl et al.,
1995; Huard et al.,
1999; Sicinski et al.,
1995; Geng et al.,
2003). Thus, it remains to be determined whether premature cell
differentiation simply generates small tissues with mostly normal shapes and
histology or significantly affects the structures.
The basic helix-loop-helix genes Hes1 and Hes5 are
essential effectors for Notch signalling, which regulates the maintenance of
undifferentiated cells (Artavanis-Tsakonas
et al., 1999; Gaiano and
Fishell, 2002; Hitoshi et al.,
2002; Honjo, 1996;
Kageyama and Nakanishi, 1997;
Selkoe and Kopan, 2003). Hes1
represses expression of the CDK inhibitor p21Cip1
(Castella et al., 2000;
Kabos et al., 2002) and
functionally antagonizes differentiation genes such as Mash1, thus
controlling both cell cycle and differentiation. We previously reported that
Hes1 and Hes5 play an important role in maintenance of
neural stem cells (Tomita et al.,
1996; Nakamura et al.,
2000; Ohtsuka et al.,
2001; Cau et al.,
2000). Here, we examined the defects of the nervous system of
embryos lacking Hes1 and Hes5 in more detail. We also
examined embryos additionally lacking Hes3, which has a similar
activity to that of Hes1 and Hes5
(Hirata et al., 2000). In
these mutants, virtually all neural stem cells prematurely differentiate into
neurons only without generating the later-born cell types, and the brain
structures are severely destroyed. These results indicate that control of the
timing of cell differentiation by Hes genes is essential not only for
the size and shape, but also for the structural integrity, of the nervous
system.
|
Materials and methods |
|---|
|
TOPSUMMARYIntroductionMaterials and methodsResultsDiscussionREFERENCES |
|---|
;
Hirata et al., 2001) were
determined, as described previously
(Hirata et al., 2001;
Ohtsuka et al., 1999).
Scanning electron microscopic analysis
Embryos were fixed in 2.0% glutaraldehyde in 0.1 M phosphate buffer for 24
hours at 4°C and then washed three times in 0.1 M phosphate buffer for 10
minutes each. They were mounted in 4% Sea Plaque GTG agarose (FMC) and the gel
was removed after cutting. Samples were dehydrated with alcohol of a series of
increasing concentrations to 100%. Embryos were then freeze-dried, mounted
onto metal stubs with carbon-conductive paint, coated with a thin layer of
gold using a sputter coater (Eiko IB-3), and viewed using a scanning electron
microscope (SEM; Hitachi S-450).
Transmission electron microscopy analysis
Embryos were perfusion-fixed with 2.5% glutaraldehyde and 2%
paraformaldehyde in 0.1 M sodium cacodylate buffer, pH 7.2. The embryos were
cut transversely into small pieces, and the samples including upper limb and
spinal cord were further fixed in fresh fixative for 3 hours at room
temperature and then overnight at 4°C. After being washed in 0.1 M sodium
cacodylate buffer, the specimens were post-fixed with 1% OsO4 for 2
hours on ice, stained en bloc with 0.5% uranyl acetate for 2 hours, and then
dehydrated and embedded in Epon 812. Ultrathin sections (80 nm) were cut and
examined using a JEOL JEM 2000 EX-type electron microscope operated at 80
kV.
In-situ hybridization
For in-situ hybridization, antisense strand probes were labelled with
digoxigenin, as previously described
(Hirata et al., 2001).
Histochemical analysis
Embryos were fixed, as previously described
(Hatakeyama et al., 2001).
Alternatively, embryos were fixed at 4°C in 10% trichloroacetic acid
solution for 1 hour, washed in PBS, and embedded in OCT
(Hayashi et al., 1999).
Embedded embryos were sectioned by a cryostat at 16 µm.
Immunochemistry was done, as previously described
(Hatakeyama et al., 2001),
with the following antibodies: anti-N-cadherin (BD Transduction Laboratories),
anti-RC2 (Hybridoma Bank), anti-nestin (Pharmingen), anti-TuJ1 (Babco),
anti-Ki67 (Pharmingen), anti-laminin-
1 (Chemicon), anti-ZO-1 and
anti-claudin-10, -15 and -18, which were kindly provided by Dr Shoichiro
Tsukita (Kiuchi-Saishin et al.,
2002). TdT-mediated dUTP nick-end labelling (TUNEL) assay was
performed with a detection kit (Roche).
Toxin-induced cell ablation
For pNes-DT-A and pNes-GFP, cDNAs for diphtheria toxin A subunit (DT-A)
(Yamaizumi et al., 1978) and
EGFP, respectively, were inserted between the nestin promoter and intron II, a
CNS-specific enhancer. Electroporation was performed, as previously described
(Ohtsuka et al., 2001). Square
electroporator CUY21 EDIT (TR Tech) was used to deliver five 50-ms pulses of
30 V with 950-ms intervals.
|
Results |
|---|
|
TOPSUMMARYIntroductionMaterials and methodsResultsDiscussionREFERENCES |
|---|
;
Conlon et al., 1995;
Hamada et al., 1999).
|
|
To investigate whether cell death is involved in the disorganized cell arrangement in Hes1;Hes5 double mutants, we next performed TUNEL assay. During E8.5-E10.5, there was no significant increase of TUNEL+ cells in the double-mutant spinal cord (Fig. 3A-F), indicating that the structural disorganization was not due to cell death. In addition, the floor plate (Shh+), V3 interneurons (Sim1+), V0 interneurons (Evx1+), D1A interneurons (Lhx2+), and the roof plate (Wnt1+) were generated in the double-mutant spinal cord as in the wild type (Fig. 3G-P), suggesting that the dorsal-ventral patterning is mostly normal in the absence of Hes1 and Hes5, despite the severe morphological abnormalities.
|
|
|
), as well as the adherens junction molecule N-cadherin
(Hatta and Takeichi, 1986),
were expressed at the apical surface of neuroepithelial cells of both the wild
type and the double mutant (Fig.
6G-L and data not shown). Thus, the structural integrity of the
neuroepithlium was maintained at E8.5 in Hes1;Hes5 double
mutants.
|
|
1 was expressed at the
basal boundary (Fig. 8I-K).
However, in the double mutant, laminin-1 expression was lost or
severely disorganized in the ventral region, where radial glial cells
(nestin+) were depleted (Fig.
8M-O), while the expression was still intact at the dorsal
boundary, where radial glial cells still remained
(Fig. 8M-O). Thus, premature
loss of radial glial cells led to defects of the basal lamina. In-situ
hybridization analysis demonstrated that laminin-1 mRNA was expressed
in the ventricular zone of the wild type, where cell bodies of radial glial
cells were present (Fig. 8L),
as previously described (Thomas and
Dziadek, 1993). By contrast, expression of laminin-1 mRNA
was undetectable in the ventral spinal cord of the double mutant
(Fig. 8P). These results
indicate that the loss of radial glia leads to disruption of the basal lamina,
allowing neurons to escape into the surrounding regions. Taken together,
radial glial cells are essential for the structural integrity of the nervous
system by forming the apical and basal barriers.
|
). We
injected pNes-DT-A into the ventricle of embryonal telencephalon at E13 and
performed electroporation, which introduced the vector into the cells on the
plus side. To identify the transfected region, we co-injected the vector for
GFP expression under the control of the CMV promoter/enhancer (pCL-GFP)
(Fig. 9D), which allowed
ubiquitous GFP expression (Fig.
9A). After five days (E18), introduction of pCL-GFP alone stained
both radial glia and neurons (Fig.
9O) and did not affect expression of the apical junction molecule
ZO-1 (Fig. 9Q, arrowheads), the
basal lamina (laminin 1) (Fig.
9N, arrowheads) or neuronal arrangement (NeuN)
(Fig. 9R). By contrast, when
pNes-DT-A was introduced, we found many TUNEL+ cells only in the
ventricular zone after 2 days (E15) (Fig.
9E-G), indicating that the pNes-DT-A vector specifically killed
nestin+ radial glial cells. Furthermore, after five days (E18), the
electroporated region had lost radial glial cells (nestin+)
(Fig. 9V,V', arrowheads)
while it contained a small number of GFP+ neurons
(Fig. 9T,T'), which were
probably nestin-negative differentiating neurons at the time of
electroporation. This region lost expression of ZO-1 at the apical side
(Fig. 9W, arrowheads) and
laminin 1 at the basal side (Fig.
9X, between the two arrowheads). Instead of radial glial cells,
the ventricular zone was occupied by ectopic neurons (NeuN+), which
were scattered into the ventricle (Fig.
9Y,Y', arrowheads). Furthermore, the cortical lamination was
destroyed with rosette-like structures, and some neurons protruded into the
outer region through the area that lacked laminin 1 expression
(Fig. 9U,X,Y). These
abnormalities were very similar to those of Hes1;Hes5 double-mutant
spinal cord, supporting the notion of the important roles of radial glia in
maintenance of the structural integrity.
|
), was expressed normally in Hes1;Hes5
double-mutants, suggesting that the initial eye specification occurred in the
double mutant (Fig. 10J).
However, the downstream homeodomain genes Pax2, which specifies the
optic stalk (Torres et al.,
1996), and Chx10, which regulates retinal formation
(Burmeister et al., 1996), were
not expressed in the double mutant (Fig.
10K-N), suggesting that accelerated neuronal differentiation may
hamper Rx-induced eye specification. Furthermore, the ganglionic
eminences were not properly formed due to accelerated neuronal differentiation
in Hes1;Hes5 double mutants (Fig.
10B, compare with Fig.
10A, arrowhead). Thus, the normal timing of cell differentiation
is essential for organization of proper structures such as the optic vesicles
and the ganglionic eminences.
|
). At
E8.0, like Hes1, Hes3 was widely expressed in the nervous system
(Fig. 11A,B,I) while
Hes5 was not (Fig.
11C). At E8.5-9.5, Hes3 expression occurred widely
(Fig. 11J,K) but was
restricted to the medial to dorsal region
(Fig. 11F,L), while
Hes5 and Dll1 expression started in the ventral to medial
region (Fig. 11G,H). After
E9.5, Hes3 expression is downregulated except for the isthmus
(Hirata et al., 2001). In
Hes1;Hes5 double mutants, Hes3 expression was not
significantly affected (Fig.
11K-M).
|
|
Discussion |
|---|
|
TOPSUMMARYIntroductionMaterials and methodsResultsDiscussionREFERENCES |
|---|
|
Radial glial cells form intercellular junctions at the apical side
Previous morphological analyses show conflicting results about the presence
of the tight junction (Aaku-Saraste et al.,
1996; Bancroft and Bellairs,
1975; Decker and Friend,
1974; Duckett,
1968; Hinds and Ruffett,
1971; Møllgård et
al., 1987; Revel and Brown,
1975). It was previously shown that, during neurulation,
expression of the tight junction molecule occludin is lost
(Aaku-Saraste et al., 1996). In
the present study, however, we found that the tight junction did exist at the
apical side of the neural tube on TEM analysis and that the tight junction
molecules claudins were expressed by radial glial cells on immunohistochemical
analysis. Thus, it is most likely that, even after neurulation, radial glial
cells are anchored at the apical side by the tight junction as well as by the
adherens junction. We speculate that a single strand junction identified by
the freeze-fracture method
(Møllgård et al.,
1987) may correspond to a claudin-based tight junction. Further
analysis is required to determine the features of the tight junction of the
embryonal nervous system.
It was previously shown that blockade of N-cadherin activity by specific
antibody or gene inactivation destroys the laminar structure of the nervous
system, indicating an essential role of N-cadherin in maintenance of the
nervous system morphology (Bronner-Fraser
et al., 1992;
Gänzler-Ordenthal and Redies,
1998; Lele et al.,
2002; Luo et al.,
2001; Masai et al.,
2003). However, because N-cadherin is diffusely expressed by
almost all neural cells including neurons, blockade of N-cadherin activity may
disrupt interactions between all these cells, making it difficult to interpret
the contribution of radial glial cells to the structural integrity. In the
present study, we showed that, although neurons still expressed N-cadherin,
loss of radial glial cells scattered many neurons out of the neural tube,
indicating that diffuse N-cadherin expression is not sufficient to keep
neurons inside the wall of the neural tube.
Radial glial cells contribute to the basal lamina formation
The basal lamina is composed of networks of glycoproteins such as laminin
and collagen IV (Timpl, 1996;
Yurchenco and O'Rear, 1994).
It was previously shown that laminin is expressed by radial glial cells
(Liesi, 1985;
Thomas and Dziadek, 1993). We
found that, when radial glial cells disappear, both laminin-1 mRNA in
the ventricular zone and laminin-1 protein at the basal side are lost
or severely downregulated. These results suggest that radial glial cells
produce, transport, and secrete laminin-1 to the basal side. The
phenotype of radial glial cell loss is very similar to that of
laminin-
1-mutant mice, which display disruption of the basal lamina and
neuronal protrusion through the meninges
(Halfter et al., 2002). Radial
glial cells thus contribute to formation of the outer barrier by expressing
laminin.
Previous studies showed that the collagen IV network is produced by
surrounding mesenchymal cells but not by radial glial cells
(Thomas and Dziadek, 1993). In
addition, in-situ hybridization analysis showed that laminin-1 mRNA is
weakly expressed by surrounding mesenchymal cells next to the spinal cord.
Thus, the basal lamina is generated cooperatively at the interface by radial
glia and mesenchymal cells.
Accelerated differentiation generates neurons at the expense of the later-born cell types in the absence of Hes genes
Neural stem cells are known to change their competency over time
(Desai and McConnell, 2000).
They initially give rise to neurons and later to other cell types such as
ependymal cells and astrocytes. Ependymal cells are the internal lining of the
neural tube and carry the adherens junction
(Lagunowich et al., 1992;
Møllgård et al.,
1987; Redies et al.,
1993), while astrocytes produce laminin (Liesi et al., 1983).
Thus, in the wild type, at later stages when radial glial cells disappear,
they are replaced by ependymal cells and astrocytes.
In Hes-null mice, differentiation of radial glial cells is
accelerated. There could be two types of acceleration: (1) all cell types are
generated rapidly; or (2) only early-born cell types are generated at the
expense of the later-born cell types. In Hes-null mice, radial glial
cells prematurely differentiate into neurons only without giving rise to
later-born cell types. It is likely that it takes a certain period of time for
neural stem cells to change their competency to generate the later-born cell
types. It was previously shown that the promoter region of the
astrocyte-specific gene for glial fibrillary acidic protein (GFAP) is highly
methylated and silenced in neural stem cells at early stages of development
(Takizawa et al., 2001).
Neural stem cells at early stages are therefore refractory to inductive
signals for astrocyte differentiation. However, as development proceeds, the
GFAP promoter region is gradually demethylated, and neural stem cells gain the
competency to become astrocytes. Thus, maintenance of radial glial cells for a
certain period of time during development has two functions: increasing the
cell number; and covering a full range of competency. Accelerated
differentiation therefore leads to defects in both aspects, reduction of the
cell number and lack of later-born cell types.
|
ACKNOWLEDGMENTS |
|---|
|
Footnotes |
|---|
|
REFERENCES |
|---|
|
TOPSUMMARYIntroductionMaterials and methodsResultsDiscussionREFERENCES |
|---|
Aaku-Saraste, E., Hellwig, A. and Huttner, W. B. (1996). Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure – remodeling of the neuroepithelium prior to neurogenesis. Dev. Biol. 180,664 -679.[CrossRef][Medline]
Allen, T. and Lobe, C. G. (1999). A comparison of Notch, Hes and Grg expression during murine embryonic and post-natal development. Cell. Mol. Biol. 45,687 -708.
Artavanis-Tsakonas, S., Rand, M. D. and Lake, R. J.
(1999). Notch signaling: cell fate control and signal integration
in development. Science
284,770
-776.
Bancroft, M. and Bellairs, R. (1975). Differentiation of the neural plate and neural tube in the young chick embryo. Anat. Embryol. 147,309 -335.[CrossRef][Medline]
Bronner-Fraser, M., Wolf, J. J. and Murray, B. A. (1992). Effects of antibodies against N-cadherin and N-CAM on the cranial neural crest and neural tube. Dev. Biol. 153,291 -301.[CrossRef][Medline]
Burmeister, M., Novak, J., Liang, M.-Y., Basu, S., Ploder, L., Hawes, N. L., Vidgen, D., Hoover, F., Goldman, D., Kalnins, V. I. et al. (1996). Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat. Genet. 12,376 -384.[CrossRef][Medline]
Castella, P., Sawai, S., Nakao, K., Wagner, J. A. and Caudy,
M. (2000). HES-1 repression of differentiation and
proliferationin PC12 cells: role for the helix 3-helix 4 domain in
transcription repression. Mol. Cell. Biol.
20,6170
-6183.
Cau, E., Gradwohl, G., Casarosa, S., Kageyama, R. and Guillemot, F. (2000). Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development 127,2323 -2332.[Abstract]
Chenn, A. and Walsh, C. A. (2002). Regulation
of cerebral cortical size by control of cell cycle exit in neural precursors.
Science 297,365
-369.
Conlon, R. A., Reaume, A. G. and Rossant, J. (1995). Notch1 is required for the coordinate segmentation of somites. Development 121,1533 -1545.[Abstract]
Decker, R. S. and Friend, D. S. (1974).
Assembly of gap junctions during amphibian neurulation. J. Cell
Biol. 62,32
-47.
Desai, A. R. and McConnell, S. K. (2000). Progressive restriction in fate potential by neural progenitors during cerebral cortical development. Development 127,2863 -2872.[Abstract]
Duckett, S. (1968). The germinal layer of the growing human brain during early fetal life. Anat. Rec. 161,231 -246.[CrossRef][Medline]
Fantl, V., Stamp, G., Andrews, A., Rosewell, I. and Dickson,
C. (1995). Mice lacking cyclin D1 are small and show defects
in eye and mammary gland development. Genes Dev.
9,2364
-2372.
Fero, M. L., Rivkin, M., Tasch, M., Porter, P., Carow, C. E., Firpo, E., Polyak, K., Tsai, L.-H., Broudy, V., Perlmutter, R. M. et al. (1996). A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27Kip1-deficient mice. Cell 85,733 -744.[CrossRef][Medline]
Fujita, S. (1964). Analysis of neuron differentiation in the central nervous system by tritiated thymidine autoradiography. J. Comp. Neurol. 122,311 -327.
Gaiano, N. and Fishell, G. (2002). The role of Notch in promoting glial and neural stem cell fates. Annu. Rev. Neurosci. 25,471 -490.[CrossRef][Medline]
Gänzler-Ordenthal, S. I. I. and Redies, C.
(1998). Blocking N-cadherin function disrupts the epithelial
structure of differentiating neural tissue in the embryonic chicken brain.
J. Neurosci. 18,5415
-5425.
Geng, Y., Yu, Q., Sicinska, E., Das, M., Schneider, J. E., Bhattacharya, S., Rideout, W. M., Bronson, R. T., Gardner, H. and Sicinski, P. (2003). Cyclin E ablation in the mouse. Cell 114,431 -443.[CrossRef][Medline]
Halfter, W., Dong, S., Yip, Y.-P., Willem, M. and Mayer, U.
(2002). A critical function of the pial basement membrane in
cortical histogenesis. J. Neurosci.
22,6029
-6040.
Hamada, Y., Kadowaki, Y., Okabe, M., Ikawa, M., Coleman, J. R. and Tsujimoto, Y. (1999). Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development 126,3415 -3424.[Abstract]
Hatakeyama, J., Tomita, K., Inoue, T. and Kageyama, R. (2001). Roles of homeobox and bHLH genes in specification of a retinal cell type. Development 128,1313 -1322.[Abstract]
Hatta, K. and Takeichi, M. (1986). Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320,447 -449.[CrossRef][Medline]
Hayashi, K., Yonemura, S., Matsui, T., Tsukita, S. and Tsukita, S. (1999). Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues. J. Cell Sci. 112,1149 -1158.[Abstract]
Hinds, J. W. and Ruffett, T. L. (1971). Cell proliferation in the neural tube: an electron microscopic and Golgi analysis in the mouse cerebral vesicle. Z. Zellforsch. 115,226 -264.[CrossRef][Medline]
Hirata, H., Ohtsuka, T., Bessho, Y. and Kageyama, R.
(2000). Generation of structurally and functionally distinct
factors from the basic helix-loop-helix gene Hes3 by alternative
first exons. J. Biol. Chem.
275,19083
-19089.
Hirata, H., Tomita, K., Bessho, Y. and Kageyama, R. (2001). Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain. EMBO J. 20,4454 -4466.[CrossRef][Medline]
Hitoshi, S., Alexson, T., Tropepe, V., Donoviel, D., Elia, A.
J., Nye, J. S., Conlon, R. A., Mak, T. W., Bernstein, A. and van der
Kooy, D. (2002). Notch pathway molecules are essential for
the maintenance, but not the generation, of mammalian neural stem cells.
Genes Dev. 16,846
-858.
Honjo, T. (1996). The shortest path from the
surface to the nucleus: RBP-J 
/Su(H) transcription factor.
Genes Cells 1,1
-9.[Abstract]
Huard, J. M. T., Forster, C. C., Carter, M. L., Sicinski, P. and Ross, E. M. (1999). Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126,1927 -1935.[Abstract]
Kabos, P., Kabosoba, A. and Neuman, T. (2002).
Blocking HES1 expression initiates GABAergic differentiation and induces the
expression of p21CIP1/WAF1 in human neural stem cells.
J. Biol. Chem. 277,8763
-8766.
Kageyama, R. and Nakanishi, S. (1997). Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. Curr. Opin. Genet. Dev. 7, 659-665.[CrossRef][Medline]
Kiuchi-Saishin, Y., Gotoh, S., Furuse, M., Takasuga, A., Tano,
Y. and Tsukita, S. (2002). Differential expression
patterns of Claudins, tight junction membrane proteins, in mouse nephron
segments. J. Am. Soc. Nephrol.
13,875
-886.
Lagunowich, L. A., Schneider, J. C., Chasen, S. and Grunwald, G. B. (1992). Immunohistochemical and biochemical analysis of N-cadherin expression during CNS development. J. Neurosci. Res. 32,202 -208.[CrossRef][Medline]
Lele, Z., Folchert, A., Concha, M., Rauch, G.-J., Geisler, R., Rosa, F., Wilson, S. W., Hammerschmidt, M. and Bally-Cuif, L. (2002). parachute/n-cadherin is reguired for morphogenesis and maintained integrity of the zebrafish neural tube. Development 129,3281 -3294.
Liesi, P. (1985). Do neurons in the vertebrate CNS migrate on laminin? EMBO J. 4,1163 -1170.[Medline]
Luo, Y., Ferreira-Cornwell, M. C., Baldwin, H. S., Kostetskii, I., Lenox, J. M., Lieberman, M. and Radice, G. L. (2001). Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin. Development 128,459 -469.[Abstract]
Masai, I., Lele, Z., Yamaguchi, M., Komori, A., Nakata, A.,
Nishiwaki, Y., Wada, H., Tanaka, H., Nojima, Y., Hammerschmidt, M. et
al. (2003). N-cadherin mediates retinal lamination,
maintenance of forebrain compartments and patterning of retinal neurites.
Development 130,2479
-2494.
Mathers, P. H., Grinberg, A., Mahon, K. A. and Jamrich, M. (1997). The Rx homeobox gene is essential for vertebrate eye development. Nature 387,603 -607.[CrossRef][Medline]
McConnell, S. K. (1995). Constructing the cerebral cortex: neurogenesis and fate determination. Neuron 15,761 -768.[CrossRef][Medline]
Møllgård, K., Balslev, Y., Lauritzen, B. and Saunders, N. R. (1987). Cell junctions and membrane specializations in the ventricular zone (germinal matrix) of the developing sheep brain: a CSF-brain barrier. J. Neurocytol. 16,433 -444.[CrossRef][Medline]
Nakamura, Y., Sakakibara, S., Miyata, T., Ogawa, M., Shimazaki,
T., Weiss, S., Kageyama, R. and Okano, H. (2000). The
bHLH gene Hes1 as a repressor of the neuronal commitment of CNS stem
cells. J. Neurosci. 20,283
-293.
Nakayama, K., Ishida, N., Shirane, M., Inomata, A., Inoue, T., Shishido, N., Horii, I., Loh, D. Y. and Nakayama, K. (1996). Mice lacking p27Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85,707 -720.[CrossRef][Medline]
Ohnuma, S. and Harris, W. A. (2003). Neurogenesis and the cell cycle. Neuron 40,199 -208.[CrossRef][Medline]
Ohtsuka, T., Ishibashi, M., Gradwohl, G., Nakanishi, S., Guillemot, F. and Kageyama, R. (1999). Hes1 and Hes5 as Notch effectors in mammalian neuronal differentiation. EMBO J. 18,2196 -2207.[CrossRef][Medline]
Ohtsuka, T., Sakamoto, M., Guillemot, F. and Kageyama, R.
(2001). Roles of the basic helix-loop-helix genes Hes1
and Hes5 in expansion of neural stem cells of the developing brain.
J. Biol. Chem. 276,30467
-30474.
Qian, X., Shen, Q., Goderie, S. K., He, W., Capela, A., Davis, A. A. and Temple, S. (2000). Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28, 69-80.[CrossRef][Medline]
Redies, C., Engelhart, K. and Takeichi, M. (1993). Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain. J. Comp. Neurol. 333,398 -416.[CrossRef][Medline]
Revel, J.-P. and Brown, S. S. (1975). Cell junctions in development, with particular reference to the neural tube. Cold Spring Harbor Symp. Quant. Biol. 40,443 -455.
Selkoe, D. and Kopan, R. (2003). Notch and presenilin: regulated intramembrane proteolysis links development and degeneration. Annu. Rev. Neurosci. 26,565 -597.[CrossRef][Medline]
Sherr, C. J. and Roberts, J. M. (1999). Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9,1149 -1163.
Sicinski, P., Donaher, J. L., Parker, S. B., Li, T., Fazeli, A., Gardner, H., Haslam, S. Z., Bronson, R. T., Elledge, S. J. and Weinberg, R. A. (1995). Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82,621 -630.[CrossRef][Medline]
Swiatek, P. J., Lindsell, C. E., del Amo, F. F., Weinmaster, G.
and Gridley, T. (1994). Notch1 is essential
for postimplantation development in mice. Genes Dev.
8, 707-719.
Takizawa, T., Nakashima, K., Namihira, M., Ochiai, W., Uemura, A., Yanagisawa, M., Fujita, N., Nakao, M. and Taga, T. (2001). DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev. Cell 1,749 -758.[CrossRef][Medline]
Temple, S. (2001). The development of neural stem cells. Nature 414,112 -117.[CrossRef][Medline]
Thomas, T. and Dziadek, M. (1993). Genes coding for basement membrane glycoproteins laminin, nidogen, and collagen IV are differentially expressed in the nervous system and by epithelial, endothelial, and mesenchymal cells of the mouse embryo. Exp. Cell Res. 208,54 -67.[CrossRef][Medline]
Timpl, R. (1996). Macromolecular organization of basement membranes. Curr. Opin. Cell Biol. 8, 618-624.[CrossRef][Medline]
Tomita, K., Ishibashi, M., Nakahara, K., Ang, S.-L., Nakanishi, S., Guillemot, F. and Kageyama, R. (1996). Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis. Neuron 16,723 -734.[CrossRef][Medline]
Torres, M., Gómez-Pardo, E. and Gruss, P. (1996). Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122,3381 -3391.[Abstract]
Tsukita, S., Furuse, M. and Itoh, M. (2001). Multifunctional strands in tight junctions. Nat. Rev. Mol. Cell. Biol. 2,285 -293.[CrossRef][Medline]
Yamaizumi, M., Mekada, E., Uchida, T. and Okada, Y. (1978). One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell 15,245 -250.[CrossRef][Medline]
Yurchenco, P. D. and O'Rear, J. J. (1994). Basal lamina assembly. Curr. Opin. Cell Biol. 6, 674-681.[CrossRef][Medline]
Zimmerman, L., Lendahl, U., Cunningham, M., Mckay, R., Parr, B., Gavin, B., Mann, J., Vassileva, G. and McMahon, A. (1994). Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12,11 -24.[CrossRef][Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  A. Iulianella, M. Sharma, G. B. Vanden Heuvel, and P. A. Trainor Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord Development, July 15, 2009; 136(14): 2329 - 2334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Endo, M. A. Antonyak, and R. A. Cerione Cdc42-mTOR Signaling Pathway Controls Hes5 and Pax6 Expression in Retinoic Acid-dependent Neural Differentiation J. Biol. Chem., February 20, 2009; 284(8): 5107 - 5118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fuhrmann, A. N. Riesenberg, A. M. Mathiesen, E. C. Brown, M. L. Vetter, and N. L. Brown Characterization of a Transient TCF/LEF-Responsive Progenitor Population in the Embryonic Mouse Retina Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 432 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Havrda, B. T. Harris, A. Mantani, N. M. Ward, B. R. Paolella, V. C. Cuzon, H. H. Yeh, and M. A. Israel Id2 Is Required for Specification of Dopaminergic Neurons during Adult Olfactory Neurogenesis J. Neurosci., December 24, 2008; 28(52): 14074 - 14087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shimizu, T. Kagawa, T. Inoue, A. Nonaka, S. Takada, H. Aburatani, and T. Taga Stabilized {beta}-Catenin Functions through TCF/LEF Proteins and the Notch/RBP-J{kappa} Complex To Promote Proliferation and Suppress Differentiation of Neural Precursor Cells Mol. Cell. Biol., December 15, 2008; 28(24): 7427 - 7441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cao, S. L. Pfaff, and F. H. Gage YAP regulates neural progenitor cell number via the TEA domain transcription factor Genes & Dev., December 1, 2008; 22(23): 3320 - 3334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Androutsellis-Theotokis, M.A. Rueger, H. Mkhikian, E. Korb, and R.D.G. McKay Signaling Pathways Controlling Neural Stem Cells Slow Progressive Brain Disease Cold Spring Harb Symp Quant Biol, November 6, 2008; (2008) sqb.2008.73.018v1. [Abstract] [PDF]
|
|
|
|
|
|
J. Ninkovic, C. Stigloher, C. Lillesaar, and L. Bally-Cuif Gsk3{beta}/PKA and Gli1 regulate the maintenance of neural progenitors at the midbrain-hindbrain boundary in concert with E(Spl) factor activity Development, September 15, 2008; 135(18): 3137 - 3148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Imayoshi, T. Shimogori, T. Ohtsuka, and R. Kageyama Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline Development, August 1, 2008; 135(15): 2531 - 2541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Q. Doe Neural stem cells: balancing self-renewal with differentiation Development, May 1, 2008; 135(9): 1575 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Briscoe and B. G Novitch Regulatory pathways linking progenitor patterning, cell fates and neurogenesis in the ventral neural tube Phil Trans R Soc B, January 12, 2008; 363(1489): 57 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kokubu, T. Ohtsuka, and R. Kageyama Mash1 is required for neuroendocrine cell development in the glandular stomach. Genes Cells, January 1, 2008; 13(1): 41 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yano, T. Imaeda, and T. Niimi Transcriptional activation of the human claudin-18 gene promoter through two AP-1 motifs in PMA-stimulated MKN45 gastric cancer cells Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G336 - G343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Vanderluit, C. A. Wylie, K. A. McClellan, N. Ghanem, A. Fortin, S. Callaghan, J. G. MacLaurin, D. S. Park, and R. S. Slack The Retinoblastoma family member p107 regulates the rate of progenitor commitment to a neuronal fate J. Cell Biol., October 3, 2007; 178(1): 129 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Saarimaki-Vire, P. Peltopuro, L. Lahti, T. Naserke, A. A. Blak, D. M. Vogt Weisenhorn, K. Yu, D. M. Ornitz, W. Wurst, and J. Partanen Fibroblast Growth Factor Receptors Cooperate to Regulate Neural Progenitor Properties in the Developing Midbrain and Hindbrain J. Neurosci., August 8, 2007; 27(32): 8581 - 8592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sirko, A. von Holst, A. Wizenmann, M. Gotz, and A. Faissner Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells Development, August 1, 2007; 134(15): 2727 - 2738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fischer and M. Gessler Delta Notch and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors Nucleic Acids Res., July 14, 2007; 35(14): 4583 - 4596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yoshiura, T. Ohtsuka, Y. Takenaka, H. Nagahara, K. Yoshikawa, and R. Kageyama Ultradian oscillations of Stat, Smad, and Hes1 expression in response to serum PNAS, July 3, 2007; 104(27): 11292 - 11297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Taylor, K. Yeager, and S. J. Morrison Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems Development, July 1, 2007; 134(13): 2435 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Daudet, L. Ariza-McNaughton, and J. Lewis Notch signalling is needed to maintain, but not to initiate, the formation of prosensory patches in the chick inner ear Development, June 15, 2007; 134(12): 2369 - 2378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kita, I. Imayoshi, M. Hojo, M. Kitagawa, H. Kokubu, R. Ohsawa, T. Ohtsuka, R. Kageyama, and N. Hashimoto Hes1 and Hes5 Control the Progenitor Pool, Intermediate Lobe Specification, and Posterior Lobe Formation in the Pituitary Development Mol. Endocrinol., June 1, 2007; 21(6): 1458 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kageyama, T. Ohtsuka, and T. Kobayashi The Hes gene family: repressors and oscillators that orchestrate embryogenesis Development, April 1, 2007; 134(7): 1243 - 1251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cao, S. L. Pfaff, and F. H. Gage A functional study of miR-124 in the developing neural tube Genes & Dev., March 1, 2007; 21(5): 531 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chapouton, B. Adolf, C. Leucht, B. Tannhauser, S. Ryu, W. Driever, and L. Bally-Cuif her5 expression reveals a pool of neural stem cells in the adult zebrafish midbrain Development, November 1, 2006; 133(21): 4293 - 4303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chiba Concise Review: Notch Signaling in Stem Cell Systems Stem Cells, November 1, 2006; 24(11): 2437 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Baek, J. Hatakeyama, S. Sakamoto, T. Ohtsuka, and R. Kageyama Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system Development, July 1, 2006; 133(13): 2467 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wildner, T. Muller, S.-H. Cho, D. Brohl, C. L. Cepko, F. Guillemot, and C. Birchmeier dILA neurons in the dorsal spinal cord are the product of terminal and non-terminal asymmetric progenitor cell divisions, and require Mash1 for their development Development, June 1, 2006; 133(11): 2105 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hashimoto, X.-M. Zhang, B. Y.-k. Chen, and X.-J. Yang VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation Development, June 1, 2006; 133(11): 2201 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. V. Taranova, S. T. Magness, B. M. Fagan, Y. Wu, N. Surzenko, S. R. Hutton, and L. H. Pevny SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes & Dev., May 1, 2006; 20(9): 1187 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Duvillie, M. Attali, A. Bounacer, P. Ravassard, A. Basmaciogullari, and R. Scharfmann The Mesenchyme Controls the Timing of Pancreatic {beta}-Cell Differentiation Diabetes, March 1, 2006; 55(3): 582 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ribes, Z. Wang, P. Dolle, and K. Niederreither Retinaldehyde dehydrogenase 2 (RALDH2)-mediated retinoic acid synthesis regulates early mouse embryonic forebrain development by controlling FGF and sonic hedgehog signaling Development, January 15, 2006; 133(2): 351 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Arai, N. Funatsu, K. Numayama-Tsuruta, T. Nomura, S. Nakamura, and N. Osumi Role of Fabp7, a Downstream Gene of Pax6, in the Maintenance of Neuroepithelial Cells during Early Embryonic Development of the Rat Cortex J. Neurosci., October 19, 2005; 25(42): 9752 - 9761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Matter-Sadzinski, M. Puzianowska-Kuznicka, J. Hernandez, M. Ballivet, and J.-M. Matter A bHLH transcriptional network regulating the specification of retinal ganglion cells Development, September 1, 2005; 132(17): 3907 - 3921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lamar and C. Kintner The Notch targets Esr1 and Esr10 are differentially regulated in Xenopus neural precursors Development, August 15, 2005; 132(16): 3619 - 3630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gotz and L. Sommer Cortical development: the art of generating cell diversity Development, August 1, 2005; 132(15): 3327 - 3332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Zecchini, R. Domaschenz, D. Winton, and P. Jones Notch signaling regulates the differentiation of post-mitotic intestinal epithelial cells Genes & Dev., July 15, 2005; 19(14): 1686 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ohsawa, T. Ohtsuka, and R. Kageyama Mash1 and Math3 Are Required for Development of Branchiomotor Neurons and Maintenance of Neural Progenitors J. Neurosci., June 22, 2005; 25(25): 5857 - 5865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-K. Bae, T. Shimizu, and M. Hibi Patterning of proneuronal and inter-proneuronal domains by hairy- and enhancer of split-related genes in zebrafish neuroectoderm Development, March 15, 2005; 132(6): 1375 - 1385. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
