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NEURAL TISSUE
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The human nervous system is the most complex
structure in the known universe. No
other object, whether seen through a telescope or microscope, approaches
its complexity. As difficult as it
is to imagine, this incredibly complex structure is made up and run by cells,
such as those pictured below. These
cells, particularly the neurons, utilize a host of proteins for their unique
function in the human nervous system such as the proteins which allow them
to generate electrical potentials, respond to neurotransmitters, and produce
neuropeptides. The gene families that include these proteins
are not unique to the nervous system, nor are they unique to humans. |
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The nervous system
might have originated in primitive sensory cells which could stimulate
local muscle contraction. The ancestral
neurons might have been simpler neurosecretory
cells which would develop the ability to conduct impulses later their
evolution. Given
that gut and pituitary hormones can be made in the brain and that neuropeptides can be made outside the nervous system, there
is reason to believe that the nervous and endocrine systems are evolutionarily
linked (LeRoith, 1981). In the nervous
and endocrine systems, a variety of signals must be sent between cells.
A number of the signaling molecules found in the nervous and endocrine
systems are known in organisms which lack these systems.
Bacteria such as E. coli
synthesize a protein similar to insulin and several protozoans
are known to make peptides similar to adrenocorticotropic
hormone, β-endorphin, and dynorphin (LeRoith, 1981). Ciliates
can possess receptors for substances which effect neurons such as ACh, neurepinephrine, and epinephrine.
A mating pheromone in the protozoan
Blepharisma resembles serotonin.
The use of cAMP in signal transduction is involved in processes other
than neural function and cAMP can even serve
as an extracellular signal in slime molds (Mackie, 1990). Some plants use the signaling molecules glycine, GABA, glutamate, and ACh
(Mackie, 1990). The simple nervous
system of cnidarians includes the use of neuropeptides
(Mackie, 1990). In essence, the nervous system runs on electricity.
Thought is electrical. Remembering your grandmother, preferring one
outfit over another based on your favorite color, and recognizing the
voice of your best friend all require that neurons conduct electricity. The ability of neurons to conduct electrical
messages (action potentials) along their axons depends on their ability
to generate resting electrical potentials across their cell membranes. This is a characteristic of most cells in the
human body and many unicellular organisms as well. Some ciliates, such as Paramecium and Opalina, generate negative resting membrane potentials which,
when stimulated, produce an influx of calcium which results in a reversal
of the ciliary beat.
Membrane depolarization results in the luminescent response in
the dinoflagellate Noctiluca. Action potentials
are known in the alga Nitella, the sensitive plant Mimosa and the venus
flytrap (Prosser, 1973, p. 457). Yeast
possess a number of genes which direct vesicle movement and
Although
the ability to conduct electricity is most commonly identified with the
nervous and muscular systems, other cell types can carry electrical messages
as well. This more primitive transport
of electrical messages may provide insight into the evolution of nervous
tissue. The epithelia of ctenophores and jellyfish can
conduct electrical messages without neurons. This neuroid conduction
is known in epithelial and muscle sheets of higher animals as well (Hoar,
1983, p. 133-4). Electrical coupling
is known to occur between the embryonic cells of squid, starfish, fish,
and tadpoles. For example, in tadpole
embryos, action potentials travel through the skin before nerves develop.
Intercellular junctions (such as gap junctions) allow electrical
coupling between cells in fly salivary glands, toad bladders, mouse livers,
and malphigian tubes (Prosser, 1973, p. 461-2).
Gap junctions allow electrical flow through cardiac and smooth
muscle. Many neurons are linked by electrical synapses
and these synapses are known between neurons in worms, mollusks, and arthropods
and in vertebrates from fish through mammals. (Prosser,
1973, p. 483). The following images are of multipolar mammalian neurons. |
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Cnidarians possess two types of nervous
cell: sensory and deeper ganglion cells.
Ganglion cells synapse with each other and with muscle cells. The neurosensory cells
seem to be the more primitive of the two since they are less differentiated
(they lack dendrites, for example) and they are very abundant in lower
vertebrates. Examples of neurosensory cells in higher animals include the receptor
cells of parietal and lateral eyes (including rods and cones), infundibular cells in fish, and olfactory neurons. In humans,
only the receptor cells of the olfactory epithelium and retina are of
this type. In cnidarians, ganglion cells possess both
Nissl substance and dendrites. These neurons are considered as primitive since
they lack myelin and impulses are transmitted slowly. Only in bilateran
animals do neurons transmit impulses in only one direction and possess
both dendrites and axons (Ariens). Autorhythmic behavior of neurons in which neurons can initiate
action potentials on their own is known in both vertebrates and invertebrates.
(Hoar, 1983, p. 305). Flatworms are the most primitive bilateran animals and their nervous systems possess a number
of features known in higher animals. Unipolar,
bipolar, and multipolar neurons are known in
the most primitive flatworms, the acoels (Rieger,
from Harrison, 1991). Higher flatworms possess multipolar
neurons with dendritic spines and soma exterior
to axons, electrical synapses, tetrodotoxin
sensitive sodium channels, voltage-gated fast sodium channels, dark adaptation
of the eye, habituation, cells similar to hypothalamic neurosecretory
cells, and the use of NE, E, serotonin, ACh, and neuropeptides
in signaling (Sarnat, 1985) Nitric oxide and nitric oxide synthase are known in flatworms and higher animals but not
in cnidarians (Tandon, 2001). One type of neuron has apparently evolved
only recently in the human lineage. The
spindle cells of the anterior cingulate
gyrus of the brain (layer Vb)
is known to exist only in higher primates. These neurons only form clusters in humans and
chimps. They are involved in the
control of meaningful vocalizations in THE GENES WHICH CAUSE THE DEVELOPMENT
OF NEURONS What genes allow cells to differentiate into
neurons? What genes guide the
early development of the nervous system?
There are many, only a few of which are given here. It turns out that many of the genes which are
essential for the development of human neurons are not unique to neurons,
nor are they unique to humans. Many
of these genes are members of gene families which evolved prior to the
evolution of animals with nervous systems. Of 116 genes known to be involved in the
development of the brain and nervous system of flatworms, more than 95%
were shared with higher bilateran animals such
as nematodes, flies, and humans. Homologs of all 116 existed in humans. Homologs of about
a third of these genes existed in organisms which lack a nervous system,
such as yeast (Mineta, 2003).
These shared genes include FGF, noggin, frizzled (a Wnt receptor), immunoglobulin/cadherin family members, otx, neuropeptide
Y, NCAM, BMP receptors, and rhodopsin (Mineta, 2003). Members
of the Wnt
gene family are involved in the formation of the vertebrate brain and
also in the regeneration of planarian brain (Marshal, 2003). apterous is a member of the
LIM-homeodomain family which possesses 2 zinc
finger-like domains in addition to its homeodomain. Both apterous and mammalian homologs are
expressed in nerve cords, eyes, brains, limbs, and olfactory structures.
The human gene can replace the activity of apterous
in the body of the fly (Rincon-Limas, 1999). There is a new family of genes (C. elegans unc-76)
known to affect axonal growth in nematodes and humans. Mutations affect the formation of fascicles
and nerve cords (Bloom, 1997). Tunicates
possess genes involved in the induction of neural tissue and for neural
function which link them to vertebrates rather than protostomes
(such as a greater diversity of Bmp
and Wnt
signals, the gene Nodal, SCO-spondin, noelin, and rhodopsin photoreceptors related to deep brain/pineal opsins of vertebrates) (Dehal, 2002).
Mutation of the nou-darake (Djndk) gene
in planarians caused an ectopic brain to form
in the trunk region (Mineta, 2003). A unique group of important embryonic cells
called neural crest cells were a vertebrate innovation. Many
of the characteristics which set vertebrates apart from more primitive
chordates are determined by these neural crest cells. Neural crest cells develop into a number of
cell types including sensory neurons, adrenergic neurons, cholinergic
neurons, Rohon-Beard cells, satellite cells, and glial
cells. As a result, the neural
crest contributes to spinal ganglia, the sympathetic and parasympathetic
divisions of the ANS, and brain, among other structures (Hall, 1999). In tunicates, there is evidence of a protoneural crest in the pigmented cells along the neural
tube (Hall, 1999). Although there
are no neural crest cells in tunicates, the expression of the snail gene
family member, Hrsna,
indicates that some of the characteristics of neural crest cells may be
present. (Meinertzhagen, 2001).
While Amphioxus lacks neural crest cells, it expresses many of the important
genes involved in the differentiation of vertebrate neural crest cells
in the region of the junction between the neural plate and the non-neural
ectoderm. Thus, it appears that
vertebrate neural crest cells employed genes which were already present
in vertebrate ancestors (Ahlberg, 20-5). The genes required to form the neural crest
did not appear suddenly in vertebrates.
Neural crest induction involves genes such as BMP, chordin,
FGF, TGF (at Hensen’s node), WNT, Shh,
dorsalin, odd-paired (a Drosophila pair rule
gene), and the snail zinc finger gene.
Many of these genes perform other functions as well and are known
(or, at least, members of their gene families are known), in more primitive
animals which lack neural crest cells.
As brains became more complex, additional
proteins were recruited to achieve this complexity. A significant feature of the mammalian cerebrum
is its organization into layers. The
protein reelin is involved in a number of neural
functions in amniotes such as neuronal migration to form layered regions
of the cerebral cortex, synapse formation in the hippocampus, and axonal
growth. Reelin
is also expressed throughout the lamprey brain (Perez-Costas,
2002). Although there have been
observations of molecular differences between human and chimp brains,
many correspond to varying level of a protein’s expression rather than
the existence of new proteins. There
are a large number of genes which are more highly expressed in the brains
of humans than those of other primates ( Sialic acids are important in deuterostomes. Most mammals, including all of the great apes,
possess the sugar N-acetylneuraminic acid (a
sialic acid) at the ends of glycoproteins,
both soluble and those of the cell membrane.
Humans lack this sugar because of a mutation in the human CMP-N-acetylneuraminc acid hydroxylase
gene. The human gene CMP-N-acetylneuraminc acid hydroxylase
possesses a deletion which caused a frameshift
mutation in the gene, rendering it a pseudogene. It is unknown what effects this mutation had
on human evolution, if any, but it may be relevant that brain tissues
of non-humans typically express low levels of sialic
acid, even when levels in the rest of the body are high. If sialic acid expression
is in some way a detriment to neural functioning, it may be that the loss
of its expression had an impact on hominid brains. Two neanderthal
fossils have also been shown to lack this sugar (Chou, 1998; Chou, 2002). In mice, there is a gene which codes for
an RNA molecule which is not translated into protein and is expressed
only in the nervous system. It
is not known in any other group of mammals.
It arose when a tRNA gene for alanine was integrated
into a new site (Kuryshev, 2001). In the genomes of anthropoid primates, a small
non-messenger RNA is expressed in the brain (Kuryshev,
2001). THE GENES NECESSARY FOR NEURON FUNCTION A neuron’s ability to create resting and
action potentials rests in its ability to transport ions, particularly
potassium and sodium ions. Potassium
channels are ancient proteins which evolved in organisms long before the
ability to transmit electrical messages.
Prokaryotes (eubacteria and archea) are known to possess potassium channels and these
channels are homologous to those found in eukaryotes (Jiang,
2002). Eukaryotic channels retain their function when the eukaryotic channel
pore is replaced by the pore from prokaryotic channels (Lu, 2001). As pictured below, the potassium channel is
not only the simplest of the voltage regulated ion channels, its 6-transmembrane
region structure (with the fourth unit being the voltage-regulated portion)
is the prototype for the more complex sodium and calcium channels which
are composed of four separate homologous regions. The simplest potassium channels form tetramers
using four subunits of the same gene. (Darnell; Yellen,
2002).The potassium, sodium, and calcium voltage regulated channels are
pictured below (after Darnell, p.782). |
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The
ion channels for potassium, sodium, and calcium belong to the same ion
channel family (along with cyclic nucleotide-gated channels and several
others). Variations in potassium channel receptors can
cause heart rhythm abnormalities, hearing loss, and seizures. While eukaryotic sodium channels are large
proteins, composed of four homologous domains of a potassium-channel like
region, a simpler sodium channel is known in bacteria. It has a single domain, homologous to potassium
channels (Catterall, 2001). In vertebrates, voltage regulated sodium channels
share a common structure and are not only expressed in excitable cells
(neurons and muscle) but some nonexcitable cells
as well (such as astrocytes and Schwann
cells). While
invertebrates only have one or two genes for voltage-dependent sodium
channels in their genomes, mammals possess ten.
As with other gene families (such as the globins and the Hox genes), it appears that genome duplications at the base
of the vertebrate lineage and more recent tandem duplications of individual
genes are responsible for this expansion.
In the human genome, the genes for voltage-dependent sodium channels
are located on four chromosomes with clusters of five tandem genes on
chromosome 2 and three tandem genes on chromosome 3 (Lopreato,
2001). Variations
in sodium channel receptors can cause epileptic and other types of seizures,
heart arrhythmias, hypertension, and disorders affecting movement. G PROTEIN COUPLED RECEPTORS Neurons must be able to respond to a wide
variety of neurotransmitters, neuropeptides,
hormones, light, olfactory stimuli, taste stimuli, and other stimuli. Interestingly, most of these phenomena are perceived
by the use of the members of one gene family, the G-protein coupled receptors.
G-protein coupled receptors are used in many cell types other than
those of the nervous system and evolved very early in the history of life,
long before the evolution of animals. This superfamily
of proteins share a set of 7 hydrophobic transmembrane
regions connected by hydrophilic sections which form either intracellular
or extracellular loops. This
is a very old family found even in bacteria; bacteriorhodopsin
is homologous to GPCRs of higher organisms although
exon shuffling has changed the order of the transmembrane regions. Gene
duplication had produced many of the subfamilies of the G proteins (Suga,
1999). This family of receptors is actually the
largest gene family known in vertebrate genomes (including that of humans).
These receptors mediate the activity of most neurotransmitters
and neuropeptides in addition to serving as
receptors in the cells which perceive taste, smell, and sight.
The use of these chemical messages and the G protein coupled receptors
which perceive evolved long before the complex nervous systems of higher
vertebrates. Serotonin, enkelphans,
and endorphins are known in flatworms (Rieger,
from Harrison, 1991). Echinoderm genomes include the GPCR receptors for oxytocin, endothelin/bombesin.neuromedin, CCK/gastrin, orexin, TRH, tachykinin, galanin, RFamide, prolactin-releasing hormone, and gonadotropin (Burke, 2006). Echinoderms possess a number of the enzymes involved in neurotransmitter production shared by vertebrates. These include enzymes involved in the metabolism of serotonin (tryptophan hydroxylase, AADC), dopamine (monamine oxidase, COMT), NO (nitric oxide synthase), noradrenaline, GABA, histamine, and Ach (Burke, 2006). Although noradrenaline is known in echinoderms, adrenaline may be limited to vertebrates (Burke, 2006).Hemichordates,
for example, utilize ACh and NE as neurontransmitters (Benito, form Harrison 1997, p. 98) and jawless
fish add GABA is an inhibitory neurotransmitter and glutamate as an excitory neurotransmitter (Hardisty,
p. 328). Both neuropeptides
and their receptors have been conserved through evolution. Neuropeptides serve
as neuromodulators in vertebrate and invertebrate
nervous systems and can function as neurotransmitters in invertebrates. In C.
elegans, about 130 putative receptors for neuropeptides have been identified. Some of the neuropeptides
involved have not yet been found in vertebrates. In mammals neuropeptides
function in a variety of neural pathways, including those involving feeding
and sleep. There are more than 60 neuropeptides
in the mammalian brain; most of them act through G-protein coupled receptors
(Nathoo, 2001). G protein coupled receptors are the receptors
for all of the following signaling molecules in the nervous system. DOPAMINE The neurotransmitter dopamine is involved
in the perception and pursuit of pleasure.
It is involved in almost every type of addiction and dopamine treatment
can decrease addiction. Its release
increases sex drive and is a factor in orgasm. There are several dopamine receptors in the
human genome whose variations (including those of DRD4, one of the most
variable human genes known) have been shown to be a factor in schizophrenia,
recurrent major depression, adolescent emotional disorders, alcoholism,
Parkinson-like disorders, scores
on personality tests related to novelty
seeking. EPINEPHRINE
Epinephrine is not
only a neurotransmitter, but it also functions as a hormone when released
from the adrenal glands during the fight or flight response. Amphetamines resemble NE. Variations in epinephrine receptor genes may
affect blood pressure, in basal metabolic rate, obesity, and
susceptibility to congestive heart failure. GABA
(gamma amino butyric acid) GABA is the major inhibitory neurotransmitter
of the vertebrate brain. More than
a dozen genes code for the subunits which can be combined to form the
receptor protein. One cluster on
chromosome 15 possesses the GABAR genes B3—A5—G3 and duplications of this
cluster seem to have given rise to the cluster on 5q34 containing the
genes B2—A6—A1—G2 and the cluster on 4p12 containing the genes B1—A4—A2—G1. Variations in GABA receptor genes have been
linked to epilepsy, bipolar disorder, insomnia, autism, and febrile seizures. GLUTAMATE
Glutamate
is the major excitory neurotransmitter in the
mammalian brain. Many glutamate
receptors function in learning. The
glutamate receptors expressed in insect muscle are the functional equivalents
to nicotinic acetylcholine receptors in vertebrates (Schuster, 1991). OPIOID
FAMILY Opioids are signals
which function in pain stimuli, feeding, sexual behavior, learning, thermoregulation,
development, and the physiology of the cardiovascular and respiratory
systems. The opioid met-enkalphin promotes cell
proliferation in several bacteria and protists
which possess opioid receptors (Zagon,
1992; Danielson, 1999). Opioid-like peptides
known from arthropods, mollusks, and annelids. Pordynorphin and large
peptide precursors of opiates seem to exist in mollusks (Stefano, 1998;
Darlison, 1997). Enkalphin and POMC
are known in several non-amniotes, including aganthans. The duplication of the ancestral gene preceded
craniates. Proorphanin
seems to have resulted from an early duplication of the gene for proenkalphin in gnathostomes. Another duplication of the proenkalphin gene produced prodynorphin
in the lineage which produced sarcopterygians
and tetrapods (Danielson, 1999). The skin of amphibians can possess a number
of opioids which act on μ and δ opioid receptors (Schmidt, 1997). |
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SEROTONIN
The neurotransmitter serotonin inhibits sex drive and orgasm;
promotes contentment, causes cravings for sweets and has been used to
treat depression, obsessive-compulsive disorder, panic, anxiety, PMS. Receptors for serotonin are involved in the
regulation of sleep, appetite, thermoregulation, pain, and sexual drives. TRACE
AMINES While
invertebrate nervous systems use biogenic amines such as tyramine,
b-phenylethylamine, tryptamine, and octopamine as neurotransmitters,
their role is not yet clear in vertebrate nervous systems.
In vertebrates, the effects of the biogenic amines norepinephrine,
dopamine, and serotonin are mediated through G-protein coupled receptors. Mammalian nervous systems possess GPCRs which interact with these trace amines as well whose
receptors belong to a family of GPCRs (TA1 through
TA15) whose function is not well understood (Borowsky,
2001). NEUROPEPTIDES In addition to a variety of neurotransmitters,
nervous systems utilize a variety of neuropeptides. The
human nervous system uses many of the same neuropeptides
found in the nervous systes of invertebrates. Cnidarians produce FMRFamide-like
peptide, oxytocin/vasopressin, and other peptides
(Thorndyke, ). Cells
of a sea anemome are depicted below. |
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FMRF and somatostatin, are known in
flatworms (Rieger, from Harrison, 1991). A large number of peptide signals had evolved
prior to the division of the coelomate lineages. Evidence indicates that mollusks (such as the
slug in the following image) synthesize vasopressin, vasotocin,
oxytocin, CRF, ACTH, αMSH,
enkephalin, dynorphin,
somatostatin, substance P, glucagons, insulin, secretin, gastrin, calcitonin, VIP, GIP, PP, FMRRamide,
AKH, dopamine, serotonin, histamine, and octopamine
(Thorndyke, ). |
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Protochordates
synthesize bombesin, calcitonin,
β endorphin, enkephalin, gastrin/CCK,
glucagons, insulin, LHRH, motilin, αMSH, neurotensin, PP, prolactin, secretin, somatostatin, substance P, VIP, serotonin (Thorndyke, ). Tunicates possess genes for all major peptide
hormone receptors (such as insulin and gonadotropins),
except growth hormone (Dehal, 2002). To date, GnRH (two
forms), somatostatin, neuropeptide
Y, and tachykinin are known to be produced in
the lamprey brain. GH, ACTH, MSH-A,
MSH-B, NHF (nasohypophysial factor), and AVT
(arginine vasotocin) are synthesized
in the lamprey in the pituitary (Sower, 2001).
Somatostatin is
expressed in the central nervous system, pancreas, intestine, and stomach
where it functions as a hormone or neuromodulator. The amino acid sequence is identical from jawless
fish through mammals. A second
somatostatin gene (termed cortistatin
in mammals) is known in actinopterygians, sarcopterygians, amphibians, and mammals (Trabucchi, 1999). Neuropeptide Y
(NPY), gut endocrine peptide YY (PYY), pancreatic polypeptide PP (PP)
and pancreatic polypeptide PY (PY) are all composed of 36 amino acids
(except in chicken PYY which possesses 37).
NPY-like neuropeptides have been found
in flatworms (such as the planarian in the following image), mollusks,
and tapeworms (Larhammar, 1993; Hoyle, 1998). |
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Annelid
worms synthesize dynorphin, and enkelpalin-like
substances. Insects synthesize oxytocin, vasotocin, vasopressin,
neurophysin, substance P, bombesin,
gastrin/CCK, VIP, PP, serotonin, and dopamine
(Thorndyke, ). |
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NPY
had evolved by the appearance of jawless fish and a duplication of the
NPY ancestral gene occurred before lampreys to produce NPY and PYY. Pancreatic polypeptide arose from a gene duplication
of the ancestral PYY (peptide YY) gene only in tetrapods. A duplication in some
teleosts produced the neuropeptide
PY. (Youson, 1999; Larhammar, 1993). All vertebrates possess neuropeptide Y in central and peripheral nervous systems (Larhammar, 1993). The
distribution of neuropeptide Y recognition sites
in the brains of lungfish is similar to that observed in amphibians (Vallarino, 1998). Mutations in the NPY gene cause the obesity in mice and is
involved in the control of lipid metabolism.
In humans, polymorphisms of this gene have been correlated to variations
in serum cholesterol, LDL levels, atherosclerosis, and serum triglyceride
levels. NPY also has other roles: it is expressed in
the olfactory epithelium and, in mice, affects alcohol intake. One polymorphism in humans is observed more
frequently in those who are alcohol dependent (OMIM). OXYTOCIN/VASOPRESSIN
FAMILIES Oxytocin is the
signal which induces labor in placental mammals, milk release in mammals,
and is a major factor in orgasm. Oxytocin (and the very similar signaling molecules of vasopressin,
mesotocin, conopressin,
etc.) evolved in more primitive animals. Most metazoan animals use sex
steroids in differentiation of male and female reproductive structures
and oxytocin for the majority of the acute events that occur at
these structures structures. Oxytocin and vasopressin
family members are known from 4 invertebrate phyla and all groups of vertebrates
(Youson, 1999). Cnidarians produce oxytocin/vasopressin
(Thorndyke, ). A number of peptides similar to oxytocin/vasotocin are known in invertebrates such as Arg-conopressin-S in mollusks, Lys-conopressin-G
in mollusks, cephalotocin in mollusks, annetocin in annelids, Lom-DH in
arthropods, and Stp-OLP in tunicates. Mollusk conopressin
genes are homologous to those of vasoticn/oxytocin
in vertebrtates (Hoyle, 1998; Youson,
1999; Kesteren, 1992). In worms,
annetocin functions in egg-laying and the contraction
of neprhidia (which propel both wastes and gametes)
(Ivell, 1999). The neurohypophysial
hormones of vertebrates are divided into two groups: oxytocin
and vasotocin families. Lungfish have the same oxytocin
family member, mesotocin, found in amphibians,
reptiles, and birds as opposed to the isotocin
found in teleost fish (such as the teleost
hatchling pictured below). The
vasotocin family member in lungfish, copeptin,
has two regions which are shared with amphibians rather than with teleost fish (Hyodo, 1997). |
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. Oxytocin functions
in a paracrine hormone in mammals, being produced
in the hypothalamus, pituitutary, mammary gland,
ovary, uterus, testis, and prostate. Oxytocin functions as an endocrine hormone initiating the
events of childbirth and milk ejection.
In ruminant mammals, oxytocin is secreted
from the ovary to induce luteolysis and in induces
the formation of the corpus luteum in marmosets. The processes regulated by oxytocin tend to be positive feedback mechanisms (such as
in birth, milk ejection mediated by neurons followed by recovery, and in
the deterioration of the corpus luteum, (Ivell, 1999). The cells of the posterior pituitary (which
secrete oxytocin) are depicted in the following
image. |
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The single amino acid mutation in ancestral
vasotocin which gave rise to vasopressin seems
to have occurred only in the ancestral mammals. All non-mammalian vertebrates possess vasotocin (Hoyle, 1998). TACHYKININ
FAMILY The human nervous system depends on additional
signals which evolved in more primitive organisms. Substance P, tachykinins,
and neurokinins are members of a gene family. No known invertebrate peptides are known which
belong to this family (Hoyle, 1998). Neurokinin A is
known in all tetrapods. (Hoyle,
1998). Frogs possess additional
kinin molecules. Substance P is related to kinins and is known in amphibians and sharks (Hoyle, 1998). Mammals are known to possess several members
of a tachykinin family including substance P,
neuromedin K and neuromedin L.
Other tachykinins are known in amphibians
(Kozawa, 1991). |
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GLIA While most of the study of the nervous system
typically concentrates on the function of neurons, there is a second type
of cell in the nervous system known as neuroglia. Glial cells actually
outnumber neurons and perform a variety of functions such as the creation
of the blood-brain barrier, the phagocytosis
of microbes, the creation of currents for cerebrospinal fluid, and the
production of myelin sheaths around neuronal axons. There are several genetic components involved
in the differentiation of multipotent precursor
cells into either neurons or glia which are
conserved between flies and vertebrates such as glide/gcm, Notch, and the involvement of
Helix-Loop-Helix transcription factors.
Mammalian gcma can substitute for Drosophila glide and the
fly gene can induce glial cell differentiation
in vertebrate neural cell lines (Van de Bor,
2002; Kim, 1998). Sonic Hedgehog
and Bmp proteins can induce cerebellar granule
cell precursors to differentiate into astroglia
(Okano-Uchida, 2004). Some hydra neurons are wrapped in sheaths
similar to glia (Mackie, 1990). Glia similar to astrocytes
exist in planarians (Sarnat, 1985) and
some neurons are wrapped in a glial sheath (Rieger, from Harrison, 1991). In nemertines, there
are glia-like cells associated with nerves and
near the gut. ( No myelin
is yet known in hemichordates (Benito, form Harrison 1997, p. 98). Myelin sheaths are known in arthropods but they
differ from those found in vertebrates (Ariens). In both vertebrates and invertebrates, Schwann cells may wrap many naked axons together. Saltatory conduction
has only been demonstrated in vertebrates. (Hoar, 1983,
p. 144). Tunicates possess glia-like
cells which support neurons. (Ruppert,
from Harrison, 1997, p. 470). Of
the roughly 330 cells of the tunicate brain, 70% are glial
cells (Nieuwenhuys, 2002). Like other lower chordates, there is no myelin.
Ciliated ependymal cells exist along
the neural canal, as in vertebrates (Meinertzhagen,
2001). Lancelets have at least
two types of glia: astocytes
and ependymal cells. Some
glial cells express Pit-1 which is a POU domain protein expressed in the pitutary to regulate growth hormone and prolactin
in vertebrates. The glial
cells which express this may be homologous to the ependymal
tanycytes in mammals (Candiani,
1999). Although modern jawless fish may possess axons surrounded by glial cells (a condition also known in higher vertebrates), there is no evidence of myelin in modern lamprey and hagfish (Bullock, 1984).In gnathostomes, oligodendrocytes
and astrocytes exist and the nervous system
is myelinated. (Hoar,VOl.
IV, 1970, p. 8). The major proteins
of myelin evolved early in the vertebrate lineage, given their presence
in fish (Vourc’h, 2004). Ependymal cells in teleosts retain
the ability to become neurons (Hoar,VOl.
IV, 1970, p. 9). The percentage
of cerebroside hydroxy fatty acids
in the brain lipids of coelocanths is similar
to tetrapods and unlike other fish (including lungfish) (Tamai, 1994). Astroglia with long processes are primarily known only in
primates. In bats and insectivores,
they exist but are limited to the ventral basal cortex. They can be present or absent in prosimians and |
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