Transcript 10 ectodermal organs

Histogenesis is the process by which cells and tissues
acquire functional specialization
In humans:
embryo
fetus
Cleavage  gastrulation  organogenesis  histogenesis
(2 weeks)
(1 week)
(4 weeks)
(7 months)
Organogenesis: the formation of organ rudiments to establish the basic
body plan.
Histogenesis: differentiation of cells within the organs to form specialized
tissues. Tissues are composed of cells and extracellular material that
perform a specific function.
Each specific tissue develops mainly from one germ layer.
The neural tube gives rise to the central nervous system
and contributes to the peripheral nervous system
Central nervous system: brain and spinal cord
Peripheral nervous system: all nervous tissue outside of the skull and vertebral
column.
From the time of neural tube closure to birth, approximately 250,000 neurons
are formed each minute. The CNS contains over 100 billion neurons when
complete.
How do neural cells grow and differentiate? The early neural epithelium
contains a pseudostratified layer of stem cells. The basement membrane is at
the outer edge and tight junctions form at the inner surface. Different cell types
are formed.
Development of neuroepithelium
Neuroepithelial cells differentiate to form two major types:
1. Stem cells: have a unlimited capacity for self renewal
2. Committed progenitor cells: these divide to produce 2 differentiated types:
A. Neuroblasts develop into neurons
B. Glioblasts form glial cells that can develop into astrocytes (glue that holds
neurons together), and oligodendrocytes (form myelin around neurons). The
microglia are macrophages derived from mesenchyme.
Mantle: the inner area where
neurons and glial cells
accumulate to form gray matter.
Marginal layer: area containing
axons of neurons that transmit
signals to other organs. They are
white due to the presence of
myelin = white matter.
Ependymal cells form the
ependymal layer that lines the
cavities. May be stem cells
The spinal cord develops a dorsoventral pattern
All nervous functions depend on development of complex connections
between neurons. These circuits start to develop in the embryo.
Alar plate: as neurons and glial cells accumulate in the mantle, they form
ridges on either side of the neural tube (dorsal or afferent columns). These will
develop into afferent nerves that conduct signals to the brain.
Basal plate: accumulation of cells in the ventral region produces basal or
efferent columns. These will develop into efferent neurons that carry signals to
muscles and organs (motor neurons).
The gray matter in the mantle layer is composed of cell bodies of neurons and
the white matter in the marginal layer is composed of myelinated axons. The
floor and roof plates are composed of glial cells. What causes this pattern?
The notochord and floor plate induce the
dorsoventral pattern of neural development
To examine whether ventral columns were induced by adjacent tissue, an
extra notochord was grafted to the side of the developing neural plate.
This created an extra floor plate and
ventral column, suggesting that it
induced these structures.
If the notochord was removed, no ventral
column or floor plate developed,
consistent with the above idea.
It is believed that the notochord first
induces the floor plate and the floor plate
then induces ventral columns. This was
confirmed by grafting a floor plate, which
also induced efferent nerves.
What is the molecular nature of this
inducer of dorsoventral patterning?
Sonic hedgehog (shh) induces the dorsoventral pattern
Sonic hedgehog (shh) is a gene that
is expressed in the notochord at first
and later in the floor plate. Mice that
lack shh fail to develop floor plates in
the CNS.
Shh is a secreted glycoprotein that
induces a gradient that is high near
the floor plate and progressively
lower in dorsal regions.
Shh initially induces neural plate
cells to form floor plate. Other
signals from the dorsal ectoderm
direct the dorsal columns and the
roof plate.
Different levels of shh appear to
specify different types of neuron
differentiation.
Different concentrations of shh induce distinct types of neurons
In the developing spinal cord, the floor plate produces shh and creates a
concentration gradient. Motor neurons develop closest to the floor plate, type
2 interneurons are next, followed by type 1 interneurons.
To see whether the shh gradient is really important, isolated cells from neural
tubes were cultured in various concentrations of shh. Cells were stained with
antibody specific for floor plate, motor neurons, or type 1 or 2 interneurons.
Bone morphogenetic protein released by the dorsal ectoderm and roof plate
has an analogous function in generating the dorsal columns
How does the brain develop?
The initial stages of brain development are similar to spinal cord (neurulation
and establishment of the dorsoventral pattern. The brain becomes more
complex as the central canal expands to form four fluid filled ventricles.
After 4 weeks, the human brain has 3
regions, the prosencephalon,
mesencephalon, and rhombencephalon.
By 5 weeks the prosencephalon divides
into telencephalon (2 outpockets that
will become the cerebral hemispheres
surrounding the 1st and 2nd ventricles)
and the diencephalon which forms
around the 3rd ventricle.
The rhombencephalon forms the
metencephalon in the anterior and the
myelencephalon in the posterior. The
myelencephalon surrounds the 4th
ventricle.
Flow chart showing brain development
Brain of a four month old fetus
Telencephalon: forms the cerebral hemispheres with 1st and 2nd ventricles
Diencephalon: forms the posterior pituitary gland (infundibulum), the
thalamus (sleep), and hypothalamus (homeostasis) with the 3rd ventricle
Mesencephalon:midbrain
Metencephalon: forms the cerebellum (balance and muscle tone) and pons
Myelencephalon: forms the medulla (reflexes)
Neural crest cells arise during neurulation
Neural crest cells: These cells arise from both dorsal epidermis and neural
plate. They migrate throughout the body. Neural crest cells form a variety of
cell types including cartilage, pigment cells of skin, neurons, smooth
muscle cells, and adrenal medulla.
Migration staging area: the cells
originate at the crests of the neural
folds during neurulation. Both
epidermal tissue and neural tissue
contribute to this lineage.
Slug: a regulatory gene that is
expressed as neural crest cells start to
leave the staging area. Slug appears to
alter expression of cell adhesion
molecules (cadherins) and it causes
dissociation of desmosomes on neural
crest cells.
Neural crest cells form a variety of tissues
The fate of neural crest cells has been mapped by a number of techniques
(radioactive tracers, transplants from pigmented species to albinos). There
are 2 patterns of migration in the trunk region:
Dorsolateral path: enter skin and form melanocytes
Ventral path: form afferent neurons of dorsal route ganglia, sympathetic
and parasympathetic ganglia, and adrenal medulla
Neural crest cells help to
form addition structures
in the head such as
bones, connective tissue,
eyes, ears, and teeth.
They also help to form
blood vessels and
connective tissue in the
trunk
How do neural crest cells differentiate into many tissues?
Pluripotency hypothesis: each
neural crest cell has the potential
to form any or all structures.
Inductive signals from adjacent
tissue determines their fate.
Selection hypothesis: the neural
crest contains a mixed population
of predetermined cells. Each cell
has only one possible fate and it
migrates according to this fate.
The real truth may lie between these two extremes.
Clonal analysis: when individual neural crest cells are placed in culture, it
is clear that a single cell can give rise to others that differentiate into
multiple cell types (pigment cells and neurons). Premigratory cells have a
wider potential than do the cells that have already started to migrate. They
may become partially differentiated as they migrate.
Pluripotency of neural crest cells in vivo
By injecting migrating neural crest cells with red fluorescent dye, it was
possible to trace their fate. Multiple cells were injected and their fate was
analyzed after several days. The structures that they formed were
determined by staining with specific antibodies (ie dorsal route ganglia).
Some red neural crest cells participated in dorsal route ganglia, others
formed parts of sympathetic ventral route ganglia, pigment cells, or adrenal
medulla. The cells appeared to be pluripotent in vivo.
Premigratory cells had a greater potential to form different structures than
migrating cells. Thus, differentiation appears to accompany migration.
What are the molecular signals that control
differentiation of neural crest cells?
Extracellular matrix (ECM): neural
crest cells constantly extend
filopodia to feel the ECM.
Pieces of filter were placed in an
embryo at the dorsolateral or
ventral pathways. After the filters
absorbed ECM, they were
removed to a culture dish and
allowed to interact with neural
crest cells.
Dorsolateral ECM induced
melanocytes and yellow pigment
cells. Ventral ECM induced
neurons. No matrix allowed the
cells to remain undifferentiated.
Polypeptide growth factors also stimulate
Differentiation of neural crest cells
1. Steel factor: a polypeptide growth factor produced by skin cells that acts
with the c-kit receptor on neural crest cells. Mutant mice that produce less
steel factor appear steel gray rather than black because they have fewer
melanocytes.
Loss of the c-kit receptor leads to areas of skin that lack pigmentation, white
spotting in animals. The same condition leads to similar symptoms in
humans, called Piebaldism.
2. Endothelins: growth factors that are important in recruiting development
of melanocytes and parasympathetic nerves in the gut. Mice that are
deficient in endothelin-3 or its receptor, EDNRB, show unpigmented regions
of skin and distention of the large intestine. The latter is due to lack of
parasympathetic neurons that induce peristaltic movements.
A similar condition occurs in humans due to mutation of the EDNRB
receptor. Hirschsprung’s disease is characterized by irregular skin
pigmentation and chronic severe constipation.
3. Transforming growth factor beta family (TGF-bs): members of the TGF-b
family selectively inhibit specific types of differentiation by neural crest
cells. When neural crest cells are grown in culture, they form colonies that
contain cells with many patterns of differentiation.
When cultured with bone morphogenetic protein-2, 50% of cells become
neurons, 25% become muscle, and 25% are mixed. If the same cells are
cultured in TGF-b, all clones develop into smooth muscle. The colonies of
cells are very large in the presence of TGF-b, suggesting that this cytokine
inhibits differentiation of other phenotypes and enhances growth.
Neural crest cells are important in formation of multiple tissues and there
are several important factors that induce their differentiation.
Head ectoderm is induced to form placodes
Placodes: the epidermis covering the head is induced by underlying brain
to form dense areas composed of columnar epithelium.
Epibranchial placodes: these form along the ventral lateral region and
develop into sensory ganglia of cranial nerves.
Dorsolateral placodes: contribute to sensory ganglia and also form parts of
the eye, ear, and nose.
Ectodermal placodes and neural crest cells have common properties, such
as their ability to form sense organs, neurons, and cartilage.
The otic placode forms the inner ear
In humans, the otic placode appears by the third week on both sides of the
rhombencephalon. The otic vesicle is induced by the underlying neural tissue in
the rhombencephalon (one example of reciprocal interaction).
It invaginates to form the otic pit and then pinches off to form the otic vesicle.
Ganglion cells develop from its medial surface.
Labyrinth:the otic vesicle expands unequally and constricts in other areas to
form a complex shape. The cochlea develops to sense sound and the
semicircular canals form to serve as an organ for balance and body position.
Formation of the eye involves reciprocal interactions
Lens placode: the ectoderm invaginates in
response to signals from the optic cup
underneath. It then pinches off as a lens
vesicle. Cells elongate to fill the vesicle and
start to synthesize crystallins.
Optic cup: forms from the neural tube by
invagination. The opening (choroid fissure)
closes forming a round optic cup, an
extension of the brain.
Optic stalk: connection to the brain that is
filled with neurons to form the optic nerve.
Reciprocal interaction: the lens induces the
formation of the optic cup and the cup
regulates formation of the lens. When the
lens from a species with large eyes is
transplanted, it induces an extra large optic
cup and it also does not grow as large as
usual.
Paradoxical arrangement of rods and cones
The pigmented retina is the outer layer and the neural retina is the inner lining
of the optic cup. These cells form the neurons and the rod and cone cells that
detect light.
It is a paradoxical arrangement because the light sensitive cells are actually in
the rear of the eye behind the neurons and facing away from light! The rods
and cones are covered by layers of bipolar nuclei and ganglion cells.
Nasal placodes form the olfactory epithelium
In humans, the nasal placodes appear after the 4th week. They are induced
by the underlying telecephalon.
During the fifth week, nasal swellings appear around the placodes which
now become the two nasal pits. The pits start out far apart, but the 2
maxillary swellings grow large and push the pits to the center. The medial
parts of the nasal swellings fuse to form part of the upper lip.
Olfactory epithelium: the original lining of the nasal pit comes to rest on the
roof of the nasal cavity. It forms the epithelium that senses smell and
connects to neurons in the telencephalon. The nasal cavity becomes
continuous with the pharynx.
What can go wrong?
Cleft lip and palate
When the nasal swellings that form the upper lip and/or palate fail to fuse
properly a cleft occurs (4th to 8th weeks of gestation). You can feel the fusion
junction with your finger (indentation in upper lip) or tongue (fusion line on
roof of mouth).
Usually occurs bilaterally
The cause is unknown
Occurs in 1 of 700 babies.
Smoking, too much vitamin A or
too little folic acid in the mother
may be a factor
A parent with cleft has a
minimum 5% chance of passing
the cleft along.
An autosomal dominant genetic
condition causes a 50% chance
of cleft palate
How does skin develop and differentiate?
Epidermis: the largest derivative of ectoderm forms the outer layer of the skin.
It is an epithelium and cells are connected by desmosomes and tight junctions.
The epidermis consists initially of two layers: periderm is a temporary outer
layer and the germanative layer lies below. The germanative layer is composed
of stem cells that divide actively to produce differentiated progeny. The basal
layer develops from the germanative layer (it contains stem cells in the adult).
Spinous layer forms as cells
are squeezed out of the
basal layer. They become
large and differentiate.
Granular layer starts
making keratin granules
Cornified or horny layer is
composed of dead cells that
are filled with keratin
It takes cells about 7 days
for each cell to journey
through the skin
Hair development in humans
The underlying mesenchyme in skin forms a dermis, a layer of connective
tissue just below the epidermis. The dermis induces a variety of epidermal
structures depending on the species (feathers, hair, scales).
Hair bud: hair formation begins as a
small bud that that penetrates the
dermis. It is induced by a group of
mesenchymal cells and the hair bud
then envelopes these cells to form a hair
papilla.
Hair follicle is the entire organ
Sebaceous glands are induced to form
on the side.
The hair shaft is formed when the inner
cells of the follicle start to differentiate
and produce keratin in the form of hair.
The continued production of keratin by
the cells at the base of the shaft causes
the hair to grow longer.
Development of mammary glands
Mammary glands: these glands
develop from 2 bandlike swellings in
the epidermis called the mammary
ridges. Depending on the species, one
or more of the segments of these
ridges persist on each side. In 7 week
human embryos, the mammary ridge
extends from the armpit to the groin.
Mammary ridge: this sprouts buds that
penetrate down into the mesenchyme
to form the lactiferous ducts. The
actual milk producing glands develop
prior to the first pregnancy. The
lactiferous ducts open into a small pit
at the surface which is transformed
into a nipple.
Mammary gland development in humans
mimicks ancestral patterns
In normal development of humans, only one pair of segments in the ridge
survives, and the remaining precursors degenerate. In some individuals, the
other segments of the mammary ridge fail to degenerate, so that accessory
nipples or breasts are formed.
Primates evolved from small creatures
that nursed multiple offspring. An
extended mammary ridge would have
given human ancestors a survival
advantage. Two breasts are obviously
more adaptive for humans who normally
have only one offspring at a time.
Atavism: the occasional and abnormal
persistance of a primitive adult feature in
an evolved species (multiple mammary
glands).
It is easier to modify an older pattern of
development than to develop a totally
new pattern. This idea is a pervasive in
developmental biology.