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REVIEW / SYNTHÈSE
Developmental neurobiology of hydra, a model
animal of cnidarians1
Osamu Koizumi
Abstract: Hydra belongs to the class Hydrozoa in the phylum Cnidaria. Hydra is a model animal whose cellular and
developmental data are the most abundant among cnidarians. Hence, I discuss the developmental neurobiology of hydra. The hydra nerve net is a mosaic of neural subsets expressing a specific neural phenotype. The developmental dynamics of the nerve cells are unique. Neurons are produced continuously by differentiation from interstitial multipotent
stem cells. These neurons are continuously displaced outwards along with epithelial cells and are sloughed off at the
extremities. However, the spatial distribution of each neural subset is maintained. Mechanisms related to these phenomena, i.e., the position-dependent changes in neural phenotypes, are proposed. Nerve-net formation in hydra can be examined in various experimental systems. The conditions of nerve-net formation vary among the systems, so we can
clarify the control factors at the cellular level by comparing nerve-net formation in different systems. By large-scale
screening of peptide signal molecules, peptide molecules related to nerve-cell differentiation have been identified. The
LPW family, composed of four members sharing common N-terminal L(or I)PW, inhibits nerve-cell differentiation in
hydra. In contrast, Hym355 (FPQSFLPRG-NH3) activates nerve differentiation in hydra. LPWs are epitheliopeptides,
whereas Hym355 is a neuropeptide. In the hypostome of hydra, a unique neuronal structure, the nerve ring, is observed. This structure shows the nerve association of neurites. Exceptionally, the tissue containing the nerve ring shows
no tissue displacement during the tissue flow that involves the whole body. The neurons in the nerve ring show little
turnover, although nerve cells in all other regions turn over continuously. These associations and quiet dynamics lead
me to think that the nerve ring has features similar to those of the central nervous system in higher animals.
Résume : Hydra fait partie des hydrozoaires dans le phylum des cnidaires. Hydra est un animal modèle pour lequel,
parmi les cnidaires, il existe le plus de données sur les cellules et le développement. Je présente donc ici le développement neurobiologique de l’hydre. Le réseau nerveux chez l’hydre est une mosaïque de sous-groupes neuraux qui compose un phénotype neural particulier. La dynamique du développement de ces cellules est inusitée. Des neurones sont
produits de façon continue par différenciation de cellules souches interstitielles multipotentes. Les neurones sont continuellement repoussés vers l’extérieur en même temps que des cellules épithéliales et ils sont rejetés aux extrémités.
Cependant, la répartition spatiale de tous les sous-groupes de nerfs est maintenue. Des mécanismes capables d’expliquer
ces phénomènes, i.e. les changements dépendants de la position des phénotypes neuraux, sont proposés. La formation
du réseau de nerfs chez Hydra peut être observée dans divers systèmes expérimentaux, mais les conditions peuvent varier d’un système à l’autre. Il est donc possible de comprendre les facteurs de contrôle à l’échelle des cellules en comparant la formation des nerfs dans les différents systèmes. Les molécules de peptides reliées à la différenciation des
cellules ont été identifiées au cours d’un tri à grande échelle des molécules de peptides signalisateurs. La famille des
LPW, composée de quatre unités qui ont en commun le N-terminal, L (ou I)PW, inhibe la différenciation des cellules
nerveuses chez l’hydre. En revanche, Hym355 (FPQSFLPRG-NH3) active la différenciation. Les LPW sont des épithéliopeptides, alors que Hym355 est un neuropeptide. Il y a une structure neurale particulière, l’anneau nerveux, dans
l‘hypostome de l’hydre. Cette structure a des associations nerveuses semblables à celles des neurites. Le tissu qui entoure l’anneau nerveux ne subit pas de déplacement, malgré le flux des tissus dans le reste du corps. Les neurones de
l’anneau nerveux sont rarement remplacés, alors que les cellules nerveuses des autres régions sont continuellement
changées. Ces associations et cette dynamique lente permettent de penser que l‘anneau nerveux ressemble par certains
aspects au système nerveux central des animaux plus évolués.
[Traduit par la Rédaction]
Koizumi
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Received 30 November 2001. Accepted 15 July 2002. Published on the NRC Research Press Web site at http://cjz.nrc.ca on
15 November 2002.
O. Koizumi. Neuroscience Laboratory, Department of Environmental Science, Fukuoka Women’s University, Kasumiga-oka 1-1-1,
Higashi-ku, Fukuoka 813-8529, Japan (e-mail: [email protected]).
1
This review is one of a series dealing with aspects of the phylum Cnidaria. This series is one of several virtual symposia on the
biology of neglected groups that will be published in the Journal from time to time.
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Introduction to the nerve net of hydra:
unique features of the diffuse nervous
system
The freshwater coelenterate hydra has a simple body plan.
Like all coelenterates, it is a diploblastic animal: it is composed of two layers of epithelial cells, the endoderm and the
ectoderm. The apical end is the head and the basal end is the
foot. The head has a hypostome with the mouth opening at
the apex and several tentacles originating from the lower
part of the hypostome.
Hydra has a simple nervous system consisting of a nerve
net that extends through the body (Hadñi 1909; Burnett and
Diehl 1964; Lentz and Barrnett 1965; Lentñ, 1968). Nerve
cells are interspersed among the epithelial cells of both layers
(Fig. 1). No large concentrations of neurons such as ganglia
are observed (Lentz and Barnett 1965; Lentz 1968; Bode et
al. 1988b). The nerve net contains two types of nerve cells,
ganglion cells and sensory cells (Davis et al. 1968; Koizumi
and Bode 1991; Grimmelikhuijzen and Westfall 1995). Ganglion cells lie close to the muscle processes at the basal ends
of the epithelial cells. Sensory cells have elongated cell bodies that extend from the level of the muscle processes in an
apical direction and an elaborate ciliary cone at the apical
end of the cell body (Fig. 1) (Westfall 1973; Westfall and
Kinammon 1978; Bode et al. 1988b; Koizumi and Bode
1991; Grimmelikhuijzen and Westfall 1995).
The nervous system of hydra has several unique features.
The most remarkable of these is the multifunction of neurons. Each neuron in hydra possesses the entire repertory of
nerve-cell functions (Westfall 1973; Westfall and Kinammon
1978), i.e., the neurons are all sensory–motor-interneurons
with neurosecretory granules. For example, a sensory cell
has sensory cilia as a sensory neuron, synaptic connections
to the muscle layer as a motor neuron, synaptic connections
to neurites or the cell body of a ganglion cell as an interneuron,
and aggregations of granules in non-synaptic regions of proximal sites of the cell body as a neurosecretory cell (Fig. 2)
(Westfall and Kinammon 1978). Ganglion cells have the same
features (Westfall 1973). Moreover, as is shown in Fig. 2,
sometimes a single neuron innervates two different types of
effectors: muscle fibers and a nematocyte (Westfall et al.
1971; Grimmelikhuijzen and Westfall 1995).
Immunohistochemistry using neuropeptide antisera and
monoclonal antibodies specific to hydra neurons on whole
mounts has made it feasible to study the nerve net of hydra
(Grimmelikhuijzen 1985; Dunne et al. 1985). These studies
have shown that the hydra nerve net contains numerous subsets of neurons and that the spatial distributions are highly
position-specific (Fig. 3). Numerous subsets of neurons
containing different neuropeptides and several subsets of
neurons defined by monoclonal antibodies were noted
(Grimmelikhuijzen et al. 1982, 1990, 1995; Grimmelikhuijzen
1985; Dunne et al. 1985; Koizumi and Bode 1986, 1991;
Koizumi et al. 1988; Yaross et al. 1986). The regional distribution of each subset tends to be constant (Koizumi and
Bode 1986; Koizumi et al. 1988; Bode et al. 1988b).
Figure 4 is a diagram showing all types of ectodermal
neurons. Ganglion cells, sensory cells, and unique nerve cells,
including those of the nerve ring, are all localized together
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Fig. 1. Organization of a cnidarian epithelium and two types of
nerve cells, a sensory cell and a ganglion cell (modified from
Mackie and Passano 1968).
on the muscle sheet of one layer of ectodermal epithelia, as
shown in Fig. 1 (Mackie and Passano 1968).
Developmental dynamics of neurons: other
unique features of the diffuse nervous
system
Hydra has three types of cell lineages: an ectodermal epithelial cell lineage, an endodermal epithelial cell lineage,
and a interstitial cell lineage. The interstitial cell lineage is
composed of interstitial cells, nerve cells, nematocytes, gland
cells, and gametes (Fig. 5). Interstitial cells are multipotent
stem cells, committed precursors, and differentiating intermediates (Campbell and David 1974; David and Gierer 1974;
David and Murphy 1977; Bode and David 1978; Bode 1996).
In an adult hydra, nerve cells are produced continuously
by constant differentiation from interstitial cells (Bode et al.
1988b; David and Hager 1994). Nerve-cell production in the
nerve net is balanced by a loss of neurons at the extremities
and by the supply of neurons to young buds. Therefore, neurons are continuously changing their axial location by moving with epithelial cells either towards the apical end (the
apex of the hypostome or the tip of a tentacle) or towards the
basal end (the basal disk) (Campbell 1967a, 1976b, 1973;
Bode et al. 1986, 1988b; Bode 1992). However, the distribution of each subset of neurons expressing a certain neural
phenotype is maintained (Bode et al. 1986, 1988b; Bode
1992).
How is the constant nerve net maintained in spite of the
active growth dynamics in hydra described above? In experiments related to this question, it was demonstrated that neurons can change the expression of FMRFamide-like peptide
and vasopessin-like peptide depending upon their position in
hydra (Koizumi and Bode 1986, 1991). Moreover, it was
demonstrated that ganglion cells were converted to sensory
cells when the the neurons were moved from the body column to the hypostome (Koizumi et al. 1988).
These dynamic features of neurons in the adult hydra correspond to properties of developing nerve cells in embryos
of higher animals.
Mechanisms controlling nerve-net
formation at the cellular level
Hydra possesses several advantages for the study of nervenet formation, which can be examined in various unique
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Fig. 2. Multifunctional nerve cells in hydra. A single sensory cell has synaptic connections to the muscle sheet of an epitheliomuscular
cell, a nematocyte, and a ganglion cell. Moreover, it has sensory cilia and neurosecretory granules (drawing based on Westfall et al.
1971; Westfall 1973; Westfall and Kinnamon 1978). The arrows show synapses and their polarities.
experimental systems: regenerating, repopulating, budding, and
normal. Nerve-net formation progresses under different conditions depending on the system, therefore we can clarify
important factors at the cellular level by comparing nervenet formation (Koizumi et al. 1990; Koizumi and Minobe
1992; Minobe et al. 1995).
Regeneration system
Hydra has a high capacity to regenerate, and a completely
new nerve net appears when the new tissue regenerates. In
this case, nerve-net formation progresses with morphogenesis
of the tissue, which brings about changes in the epithelial environment of nerve precursor cells and nerve cells. In this
system, the importance of epithelial cells for the formation
of the nerve net was demonstrated (Bode et al. 1988a;
Koizumi et al. 1990; Koizumi and Minobe 1992).
Nerve-net formation during head regeneration was examined by means of immunohistochemistry, using an antiserum
against the neuropeptide RFamide. In the head of an intact
hydra, there are RFamide-like immunoreactive (RFamide+)
sensory cells at the apex of the hypostome and RFamide+
ganglion cells in the lower part of the hypostome and the
tentacle. The formation of the nerve net specific to the head
progresses in two steps during head regeneration. The first
step is the early appearance of ganglion cells at the apex.
The second step is the late appearance of sensory cells at the
apex and the simultaneous disappearance of ganglion cells
from the apex (Fig. 6). This sequential patterning corresponds to the behavior of epithelial cells as defined by a
monoclonal antibody, TS19, which binds only to ectodermal
epithelial cells in the tentacle. The labeling pattern of TS19
progresses in two steps during head regeneration. First, TS19+
epithelial cells appear at the apex, and later TS19+ epithelial
cells disappear from the apex and are present only in the ten-
tacles. The similar two-step pattern of nerve-net formation
and the appearance of tentacle-specific epithelial cells during
head regeneration suggests that they have common control
mechanisms (Bode et al. 1988a).
Nerve-net formation was examined during head regeneration
in three morphogenetic mutants, head-regeneration-deficient
mutants, budding-deficient mutants, and multiheaded mutants,
isolated by Dr. Sugiyama’s group in Mishima, Japan (Sugiyama and Fujisawa 1977). The results showed that the two
steps of nerve-net formation are distinct processes that can
change independently. Moreover, abnormalities in the behavior of tentacle-specific epithelial cells in the mutants correspond well to the formation of their nerve net (Koizumi
et al. 1990). These data strongly suggest that a common
mechanism controls the pattern of nerve-net formation and
tentacle-specific epithelial cells.
It is possible to make hydra chimeras in which all epithelial cells are from a wild type and all nerve cells are from a
mutant or vice versa (Marcum and Campbell 1978a, 1978b;
Sugiyama and Fujisawa 1978b, 1979). Nerve-net formation
during head regeneration in these chimeras was examined to
determine whether epithelial cells or neurons are the primary
cause of abnormal nerve-net formation in mutants. The results
show that the epithelial cells are responsible for abnormalities in nerve-net formation (Koizumi et al. 1990). Nerve-net
formation in chimeric strains (produced between wild-type
and mutant strains) demonstrated that it is controlled by the
environment provided by epithelial cells during head regeneration.
All of the above experimental results suggest that interactions between epithelial cells and nerve precursor cells are
important for nerve-cell differentiation and nerve-net formation
in hydra (Bode et al. 1988a; Koizumi et al. 1990; Koizumi
and Minobe 1992).
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Fig. 3. Nerve net in hydra, visualized immunohistochemically. The patterns of the nerve nets differ depending on their position.
(A) RFamide-like immunoreactive (RFamide+) nerve net in the hypstome. View from above the hypostome, showing the dark mouth
region in the center surrounded by a large number of epidermal sensory cells. (B) RFamide+ nerve net of the upper body column.
Scale bars = 50 µm.
Repopulation system
We can examine nerve-net formation in a unique system
called the repopulation system. Many of hydra’s highly specific cell types (neurons, nematocytes, gland cells, and gametes) are part of a single lineage of cells that is continually
being renewed by proliferation and differentiation of stem
cells called interstitial cells (Fig. 5). The entire interstitialcell lineage can be removed from a hydra by various means
(Campbell 1976; Sugiyama and Fujisawa 1978a). The resulting animal is termed an epithelial hydra and is composed of
only ectodermal and endodermal epithelial cells. This viable
epithelial shell can then be repopulated by interstitial cells,
since they migrate into the depleted animal from a small
temporary graft of normal tissue (Marcum and Campbell
1978a, 1978b; Sugiyama and Fujisawa 1978b, 1979).
Using the repopulation system, therefore, neuronal differentiation and nerve-net formation can be observed in neuronfree tissue. Figure 7 shows the sequential appearance of
nerve cells in the head that was observed. Various behavioral
responses corresponding to the sequences were recovered sequentially.
This “epithelial hydra host” provides an excellent experimental system for examining the relative roles of the epithelial factors described in the previous section (Regeneration
system). Nerve-net formation in this system, in contrast to
the regeneration system, occurs without morphogenesis of
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Fig. 4. All types of ectodermal nerve cells in hydra. Neurons localized in the same place are illustrated separately in A–C. (A) Ganglion cells. (B) Nerve ring and other unique neurons. (C) Sensory cells.
Fig. 5. The three cell lineages in hydra. (A) The ectodermal epithelial cell lineage. (B) The endodermal epithelial cell lineage.
(C) The interstitial cell lineage, containing interstitial cells and
their differentiation products. Interstitial cells consist of
multipotent stem cells (I stem), committed precursor cells, and
differentiating intermediates. Nv, nerve cells; GC, ganglion cells;
SC, sensory cells; Nc, nematocyte; GL, gland cells.
epithelial tissue because the epithelial hydra host maintains
the established morphology (Marcum and Campbell 1978a;
Sugiyama and Fujisawa 1978b).
If epithelial cells indeed play an important role in producing
region-dependent nerve-cell differentiation, we would expect
nerve-cell differentiation in the epithelial hydra host to have
similar regional specificity to that of a normal hydra. However, such specificity would not be expected if neurons instead of epithelial cells are the major factor determining the
regional distribution of neurons. Instead, a random or totally
different neuron-differentiation pattern would be expected.
It has been reported that nerve-cell differentiation in epithelial hydra hosts occurs in the same region-dependent manner
as in a normal hydra, thus providing direct evidence for the
role of epithelial cells in regulating nerve-cell differentiation
(Minobe et al. 1995).
Normal (and adult) system
In an adult hydra, neurons arise continuously by differentiation from multipotent stem cells among the interstitial
cells (David and Gierer 1974; Bode and David 1978; Bode
1992). Interstitial cells committed to neuron differentiation
divide to form a pair of small interstitial cells, which in turn
divide and subsequently form neurons (Bode et al. 1990; David and Hager 1994). To compare the neuron-production
rates, animals were pulse-labeled with BrdU, and the labeling index of various subsets of neurons was measured periodically. A particular subset was identified by doublelabeling cells with an antibody against BrdU and with an
antibody against a particular type of neuron.
To analyze the kinetics of neuronal differentiation, animals initially labeled with BrdU were subsequently labeled
with an antibody against BrdU (Plickert and Kroiher 1988)
and either DB5 or RC9. BrdU (1 mM) dissolved in hydra
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Fig. 6. Reappearance of the RFamide+ nerve net during head regeneration in hydra. The numbers indicate days after decapitation.
culture medium was injected into the gastric cavity of a hydra. To measure the labeling index of neurons, labeled nuclei were visualized with a monoclonal antibody against
BrdU (mouse IgG) and the cytoplasm of neurons with the
monoclonal antibody DB5 or RC9 (both mouse IgMs). The
difference in isotypes as well as the sequence of steps reduced cross-reactivity to background levels in the doublelabeling procedure (Fig. 8) (Koizumi et al. 1992).
The epithelial hydra host is also an excellent system for
examining the relative roles of neuronal factors. Since an epithelial hydra is completely devoid of nerve cells, neuron
differentiation occurs in the absence of any influence from
existing neurons. In contrast, nerve-cell differentiation occurs in the presence of fully matured nerve cells in the normal (and adult) system. If there are differences in nerve-cell
differentiation and nerve-net formation between the repopulation system and the normal system, we can assess the role
of mature nerve cells in nerve-cell differentiation.
Other systems that can be used in the study of nerve-net
formation are the budding system and dissociation/reaggregation
system. Budding is the mode of asexual reproduction used
by hydra. A second axis formed by simple protrusion from
the body column produces the head, body column, and foot
sequentially during budding (Otto and Campbell 1977). In
the dissociation/reaggregation system, a normal hydra can
regenerate from a cell mass after being dissociated into single
cells and then reaggregated by centrifugation (Gierer et al.
1972). In both cases a normal nerve net eventually develops.
Mechanisms controlling nerve-net
formation at the molecular level
To examine the molecular mechanisms of nerve-net formation, a joint project, “Large-scale non-targeting screening
of peptide signal molecules in hydra”, has started (Takahashi
et al. 1997; Bosch and Fujisawa 2001). Takahashi et al.
(1997) developed a novel procedure for systematically isolating peptide signal molecules from hydra. Peptides were
extracted from large numbers of hydra, purified to homogeneity using high-performance liquid chromatography (HPLC)
without any biological assays. The isolated peptides were
subjected to structural analysis using automated amino-acid
analysis and then synthesized chemically, and the identity of
synthetic peptides with native peptides was confirmed using
HPLC. The synthetic peptides were then subjected to a series of biological test to examine their functions in hydra.
Using this approach, a number of peptides have been identified that regulate development in hydra in addition to neuropeptides controlling synaptic transmission and muscle contraction (Table 1) (Takahashi et al. 1997, 2000; Yum et al.
1998; Grens et al. 1999; Bosch and Fujisawa 2001; Harafuji
et al. 2001).
Among these peptides, some that control nerve differentiation in hydra were identified. Some belong to the LPW
family, and another peptide is Hym355 (FPQSFLPRGamide).
A group of 4 peptides belong to the LPW family, which
have 5–8 amino-acid residues and share the common Nterminal structure of L(or I)PW. All LPW peptides inhibit
nerve-cell differentiation in hydra (Takahashi et al. 1997). In
contrast, Hym355 activates nerve differentiation in hydra
(Takahashi et al. 2000).
Immunohistochemical analysis using antibodies to these
peptides shows that Hym355 is a neuropeptide localized in
nerve cells but LPW peptides are epitheliopeptides which
are localized in epithelial cells. Cotreatment with a LPW
peptide and Hym355 nullified the effect of both peptides,
which suggests that they act in an antagonistic manner
(Takahashi et al. 2000).
Figure 9 illustrates the sequence of nerve differentiation
and the effects of peptides. Interstitial multipotent stem cells
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Fig. 7. Reappearance of the nerve net in the repopulation system. (A) RFamide+ nerve net. (B) RC9+ nerve net. RC9 is a monoclonal
antibody specific to nerve precursor cells (interstitial cells) and ganglion cells. The time (hours or days) elapsed after nerve precursor
cells were grafted into the epithelial host is indicated. Both are views from above the hypostome.
(I stem) are committed to nerve differentiation in the body
column; the committed nerve precursor cells (I Nv) migrate
into the head and foot and then differentiate into nerve cells
(Nv) (Bode et al. 1990; Teragawa and Bode 1990; David
and Hager 1994; Bode 1996). At the same time they
differentiate into the type of neuron appropriate for the final
location (Bode 1996). Hym355 released from nerve cells
activates nerve-cell differentiation, but LPW peptides from
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Fig. 8. Double-labeling of BrdU-labeled nuclei and nerve cells using the BrdU antibody and the neuron-specific monoclonal antibody
RC9. BurU-labeled nuclei were visualized by fluorescein (green fluorescence) and nerve cells were labeled by Texas red (red fluorescence). BrdU-labeled nuclei of double-stained nerve cells appear yellow with a dual-band filter. (A) Hypostome. (B) Tentacles. Scale
bar = 50 µm.
epithelial cells inhibit it. Both might interact and act antagonistically (Takahashi et al. 2000; Bosch and Fujisawa 2001).
The next step of the study is to clarify the exact site of action. Is it commitment, migration, or differentiation?
A unique neural structure: the nerve ring in
the perihypostomal region of hydra
The nerve ring in the hypostome of hydra was observed
immunocytochemically using an antiserum against neuropeptides and neuron-specific monoclonal antibodies (Fig. 10).
The nerve ring in the mesh-like nerve net of hydra is unique.
It is a distinct neuronal complex consisting of a thick nerve
bundle running circumferentially at the border between the
hypostome and the tentacle zone. Immunolabeling showed
that the nerve ring is heterogeneous and contains at least
four different subsets of neurons. During head regeneration
and budding, the nerve ring appeared only after the nerve
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Table 1. Hydra peptides whose function was identified.
Peptide
Structure
Function
Reference
Hym323
KWVQGKPTGEVKQIKF
Morphogenesis
Foot activation
Harafuji et al. 2001
Hym346
Hym301
AGEDVSHELEEKEKALANHS
KPPRRCYLNGYCSPa
LPW family
Hym33H
Hym35
Hym37
Hym310
Hym355
Hym176
AALPW
EPSAAIPW
SPGLPW
DPSALPW
FPQSFLPRGa
APFIFPGPKVa
GLWamide family
Hym53
Hym54
Hym248
Hym249
Hym331
Hym338
Hym370
NPYPGLWa
GPMTGLWa
EPLPIGLWa
KPIPGLWa
GPPPGLWa
GPPhPGLWa
KPNAYKGKLPIGLWa
Grens et al. 1999
Morphogenesis
Tentacle formation
Cell differentiation
Inhibition of nerve differentiation
Activation of nerve differentiation
Muscle contractions
Ectoderm
Takahashi et al. 1997
Takahashi et al. 2000
Yum et al. 1998
Takahashi et al. 1997
Fig. 9. Effects of peptide signal molecules on nerve differentiation in hydra. A neuropeptide, Hym355, activates nerve differentiation, while epithelial peptides, the LPW family, inhibit it. I
stem, interstitial stem cell; I Nv, committed nerve precursor
cells; Nv, differentiated nerve cells.
Bud detachment
These associations and quiet dynamics lead us to think the
nerve ring has features that closely resemble those of the
central nervous system in higher animals.
Conclusion
net of ganglion and sensory cells had formed (Koizimi et al.
1992).
The ectoderm in the immediate vicinity of and including
the nerve ring constitutes a stationary zone that is not displaced. Tissue immediately above this zone is displaced towards
the tip of the hypostome, while tissue below is displaced
along the tentacles. Correspondingly, the production of new
neurons in the ring, measured by their differentiation kinetics, is much slower than in surrounding areas. Thus, the
nerve ring is static and stable in contrast to the dynamic features of the nerve net of hydra (Koizumi et al. 1992).
To understand a certain nervous system, both interdisciplinary and overall neurobiological study is essential. Study
of the formation of the nervous system (developmental
neurobiology) is essential in addition to studies of structure
(neuroanatomy) and function (neurophysiology, neuroethology, and behavioral physiology). In addition, studies at
various levels are desirable, from the molecular level to the
whole-animal level.
According to current overall neurobiological studies of the
nervous system of hydra, unique features of the neurons in
this primitive nervous system have appeared. Each neuron in
hydra has the general properties of a cell, while neurons in
higher animals are highly specialized. Each neuron in hydra
has a complete set of nerve functions. Each neuron has
neurites as nerve fibers, but the differences between dendrites and axons present in higher animals are not observed
in hydra.
Neurons in hydra show constant birth and death and constant displacement. They show considerable changes in phenotype under the influence of the environment. Hence, they
show active developmental dynamics and plastic properties.
Because of these properties we can use unique experimental systems, such as the regeneration, budding, repopulation,
normal, and dissociation–reaggregation systems, for studying nerve-net formation. In the near future, descriptions of
nerve-net formation in hydra will be made possible by combining studies at the molecular, cellular, and system levels.
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Fig. 10. RFamide+ nerve ring observed in the hypostome of Hydra oligactis. Scale bar = 100 µm.
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