Histogenesis of organs derived from mesoderm and endoderm

1
Histogenesis of organs derived from mesoderm and
endoderm
Endoderm endodermal derivatives consist of the
lining of the digestive tract and derivatives.
These include liver, pancreas, bladder, lungs,
and thyroid. Mesoderm a wide variety of tissues
including bone, muscle, urogenital organs
(oviducts, uterus, epididymis), circulatory
system (blood and vessels), connective tissue,
kidney, and heart. Histogenesis of endodermal
and mesodermal tissues provide examples of two
recurrent themes in developmental
biology Recapitulation the occurrence of a
phylotypic stage in development at which all
species of a phylogenetic group show an uncanny
similarity. Advanced organisms, such as humans,
often go through developmental stages that
resemble more primitive ancestors (birds or
fish). Reciprocal interaction many organs
originate from two embryonic rudiments, usually
one is epithelial and one mesenchymal. During
development, the rudiments exchange signals to
insure that both structures develop harmoniously
(lung and kidney)
2
Lateral folding in embryos creates the gut,
coelom, and amniotic cavity
In most vertebrate embryos, the endoderm
originally forms a layer adjacent to yolk or a
yolk sac cavity. Gut during development, the
flanks bend in ventrally to close the endoderm
and create the gut (seen as a section through the
middle). Coelom the mesoderm moves ventrally to
join in the middle and create the body cavity.
Amniotic cavity the amnion also moves
ventrally and to the middle to form the amniotic
sac. This surrounds the embryo.
3
Craniocaudal flexion also aids in closing the gut
Craniocaudal flexion rapid extension of the
neural plate just before closing causes the
anterior and posterior regions to flex
downward. Vitelline duct the wide opening to
the yolk sac becomes a narrow passage. Buccophary
ngeal membrane forms at the anterior end of the
gut. Cloacal membrane forms at the caudal
end. Pharynx the gut between the bucco
pharyngeal membrane and the lung bud. Foregut
the gut from the lung bud to the rudiment of the
liver and pancreas. Midgut/hindgut from the
liver to the cloacal membrane. Bending inward at
the lateral boundaries and from the anterior and
posterior is involved in initiating formation of
gut structures
4
The embryonic pharynx contains a series of arches
The development of the pharynx in humans and
other mammals actually recapitulates that of more
primitive ancestors (birds and fishes). Pharyngea
l pouch bulges in the pharyngeal endoderm that
push away the mesoderm. This induces the
formation of an overlying pharyngeal cleft in the
ectoderm. In some species, the pouches open to
form gill slits between the arches. The
pharyngeal arches were probably used by primitive
ancestors to filter food from the water. In fish,
they have developed into gills.
5
The pharyngeal arches have different fates in
humans
Outer and inner ear the first pharyngeal cleft
becomes the outer ear while while the first
pharyngeal pouch becomes the inner ear. Tympanic
membrane the eardrum develops where the first
pouch meets the first cleft. Malleus and incus 2
small bones within the ear that are essential for
hearing. They develop from the first pharyngeal
arch. Hyoid bone supporting the tongue develops
from the second arch, the larynx develops from
the third arch. Tonsil develops from the second
cleft. The thymus and parathyroid glands develop
from the third and fourth pouch.
6
The phylotypic stage of development occurs in all
species of a phylum
Recapitulation advanced vertbrates recapitulate
embryonic stages of their phylogenetic ancestors.
After the phylotypic stage, each species displays
a specialized pattern of differentiation. Why??
you once looked like a fish!
Evolution seems to modify existing patterns of
development rather than creating new ones. It is
speculated that mutation of genes that control
the phylotypic stage may prove lethal. Changing
is easier than reinventing.
7
The lung develops from endoderm
Tracheal rudiment this bud grows out of the gut
and branches to form two bronchial buds. The
bronchial buds elongate to develop into the
bronchi, and then bud many times to form the
bronchioles. Alveoli at the end of bronchioles,
small grape-like sacs develop. These alveoli are
the gas exchange tissues and they become
surrounded by small capillaries The interior of
the lung is formed from endoderm. All of the
other structures such as cartilage, blood
vessels, and connective tissue are derived from
mesoderm.
8
The mesoderm organizes into four major regions
The mesoderm lies between the sheets of
ectodermal and endodermal epithelia. It can form
epithelial structures, however, it frequently
forms mesenchyme, isolated cells surrounded by
extracellular matrix. The mesoderm organizes
into four major regions called axial, paraxial,
intermediate, and lateral plate mesoderm.
Axial mesoderm located along the dorsal midline.
It forms prechordal plate and cranial cartilage
in the head. It forms notochord in neck, trunk,
and tail. The notochord is a long rod of
connective tissue that is replaced by the
vertebral column during embryogenesis. Notochord
forms intervertebral discs.
9
Paraxial mesoderm develops into somites
Somites the paraxial mesoderm exists on both
sides of the neural tube. As the tube closes, the
mesoderm forms into small segmented structures
called somites.
Presomitic plates before the somites form, the
paraxial mesoderm exists as a long plate
stretching from Hensons node to the anterior. As
the node moves posteriorly during gastrulation,
the somites form progressively from anterior to
posterior
Somitomeres newly forming somites consist of a
whirl of mesenchyme that develops into one
somite. The left and right rows of somites are
separated by the notochord.
10
What is the mechanism for somite formation?
At least two factors are important X-Delta-2 a
ligand for a receptor called X-Notch-1. The
X-Delta-2 RNA is expressed early in Xenopus
embryos as bands in the presomitic plate. Somites
develop here immediately after expression occurs.
If the signaling pathway of X-Notch-1 is altered
experimentally, somites fail to form.
N-cadherin the somitomeres develop into somites
by changing from a solid ball of loose mesenchyme
into a hollow ball of epithelial cells. This
change is correlated with expression of
N-cadherin at the apical surface of the cells.
11
Each section of the somite forms specific
structures
The fate of cells within the somite has been
traced by labeling cells with dye or
radioactivity. It forms 4 structures
1. Sclerotome cells from the ventromedial
portion become mesenchymal and divide rapidly.
They migrate to surround the notochord and neural
tube. They form cartilage which later becomes the
vertebral column and ribs. Dermomyotome this is
what remains of the somite after the sclerotome
leaves. 2. Dermotome the outer layer of cells
migrates dorsally to form the connective tissue
below the epidermis dermis. 3. Epaxial
myotome a lip formed at the dorsomedial margin.
These cells form muscles of the dorsal trunk. 4.
Hypaxial myotome the lip at the ventrolateral
margin migrates ventrally to form the muscles of
the limbs and ventral trunk.
12
Somites differentiate in response to signals from
surrounding cells
The notochord and neural tube are necessary
survival signals. If these two structures are
surgically removed from the embryo, the somites
degenerate. There are three major origins of
differentiation signals ventralizing,
dorsalizing, and lateralizing. Ventralizing
signal this is produced by the notochord and the
floor plate of the neural tube. These structures
produce sonic hedgehog (shh) which ventralizes
the somite and allows it to form sclerotome. High
doses of shh produce sclerotome, but lower
concentrations induce myotome (analogous to the
ventralizing activity of the neural tube.
13
Dorsalizing signal the dorsal epidermis and roof
plate provide signals that dorsalize the somite.
This causes formation of epaxial myotome which
will form the dorsal muscles.
The product of the Wnt gene contributes to this
induction. The Wnt gene product binds to
receptors on mesenchymal cells and inactivates
the GSK-3 kinase. The GSK-3 kinase normally
degrades b-catenin. In the absence of GSK-3,
b-catenin and another factor, Tef-3, combine to
form a transcription factor. The target of this
transcription factor is the goosecoid gene, which
encodes Spemanns organizer. This is a strong
dorsalizing influence.
14
Lateralizing signal an inhibitory signal from
the lateral plate mesoderm causes the development
of hypaxial myotome. This mesoderm forms ventral
and limb muscles. Bone morphogenetic protein-4
(BMP-4) is a molecule that contributes to the
lateralizing signal. This is the same molecule
that antagonizes Spemanns organizer and induces
the ventral body pattern. The activity of BMP-4
on hypaxial myotome is antagonized by noggin and
chordin, which are produced within the
dorsomedial cells of the myotome.
15
Are adult stem cells just faking it?

• Adult stem cells are from mature tissue no
  ethical problems
• Recent work suggests that adult stem cells may
  not be totipotent
• When transplanted, they may just fuse with
  existing cells!
• Scientists are having some interesting and
  tense battles
• The emphasis is on shifting to work with
  embryonic stem cells
• Has the US govt dropped the ball???

16
Model of transverse patterning in somites
Ventralizing signals caused by sonic hedgehog
induce the sclerotome, which forms the vertebral
column and ribs. Dorsalizing signals induced by
the Wnt family/goosecoid contribute to induction
of epaxial myotome and dorsal trunk
muscles. Lateralizing signals due to BMP-4 may
cause the hypaxial myotome to form, producing
ventral trunk and limb muscles.
17
Sclerotome forms many types of connective tissue
Connective tissue different forms of connective
tissue exist, including cartilage, bone, tendon,
and adipose tissue. These tissues have high
levels of extracellular matrix (fibers such as
collagen and ground substance such as
proteoglycans. Fibroblasts ? fibrous tissue and
smooth muscle, chondrocytes ? cartilage,
osteoblasts ? bone, adipocytes ? fat.
Think of fibroblasts as the stem cells from
sclerotome that produce all of the other cell
types of connective tissue
18
Cartilage and bone are specialized forms of
extracellular matrix
Cartilage is produced by chondrocytes. It is
continually formed from within by secretions of
chondrocytes. These cells exist in small spaces
called lacunae. Cartilage is produced on the
outside by converting fibroblasts into
chondrocytes
Bone is formed by osteoblasts. The bone ECM
calcifies and traps the osteoblasts (which are
then osteocytes). Bone is continually remodeled
due to digestion by osteoclasts and synthesis by
osteoblasts. If degradation predominates,
osteoporosis occurs.
Bone can form from two pathways Membranous
ossification in the skull, osteoblasts directly
form bone. Endochondrial ossification most bones
form by replacement of cartilage with bone.
Osteoclasts invade and degrade cartilage and
osteoblasts fill in the spaces with new bone.
19
Myotomes make skeletal muscle
Myoblasts specialized cells in myotome (epaxial,
hypaxial, dermatome) that form skeletal muscle.
The myoblasts proliferate at first, then they
fuse to form large, multinucleate cells called
myotubes. The myotubes form skeletal muscle
cells, which are gigantic (they can be 0.1 mm in
diameter and ½ meter in length). The striated
appearance is due to the characteristic alignment
of thick and thin filaments composed of myosin
and actin. Muscle growth occurs by increase in
the size of fibers, not their overall number. The
total number of muscle fibers is attained prior
to birth.
20
Intermediate mesoderm forms the kidney
The intermediate mesoderm is located between the
somites and lateral plates.
Kidney the principle function is to eliminate
waste products. Blood is filtered through the
kidney, nutrients and serum proteins are
reabsorbed from the filtrate, and waste products
(urea) are excreted. Recapitulation Three types
of kidneys develop in vertebrates Pronephros
(probefore, nephroskidney) formed in the neck
region of all vertebrate embryos, but persists to
adulthood only in some fishes. Mesonephros
(mesomiddle) formed for much of the length of
the trunk in most vertebrate embryos. It persists
in most fishes and amphibians. Metanephros
(metaafter) the metanephros forms in the
posterior and becomes the kidneys in birds,
reptiles, and mammals.
21
The pronephros is the primitive kidney
A blood filtration unit is present, but it is
separated from the reabsorptive unit by the
coelom. Glomus a tuft of blood vessels that
projects into the coelom. The filtration occurs
here. Neprostome the filtered material is swept
through the coelom and into a funnel. Pronephric
duct the funnel is connected to a long tube that
transports nutrients and serum proteins into the
surrounding blood sinus. The pronepros is a
recycling organ that works at low blood pressure
22
The mesonephros contains nephrons
The mesonephros forms over much of the length of
the trunk in all vertebrates Nephron the
functional unit of the kidney. The glomerulus,
composed of a tuft of blood vessels, is in direct
contact with the reabsorptive unit, the
mesonephric tubule. Mesonephric tubules are
surrounded by a capillary bed that returns
reabsorbed material to the blood. Mesonephric or
Wolffian duct the individual tubules drain into
this larger duct to carry waste away.
23
The metanephros contains a counter current
exchange
The metanephros is structured like the adult
human kidney. It contains a long Loop of Henle
where most of the water can be reabsorbed by a
counter current exchange mechanism. The nephric
tubules reabsorb nutrients and the collecting
ducts carry away the waste. It is a high pressure
system. The metanephros develops from a uteric
bud that arises from the posterior of the
mesonephric duct. It forms the ureter, the calyx,
and many collecting tubules.
The other organ rudiment is the metanephrogenic
mesenchyme. It is induced by the uteric bud to
form the nephrons. Reciprocal induction.
24
Reciprocal interactions are important for
development of the metanephros
Step 1 the metanephrogenic mesenchyme induces
the adjacent mesonephric duct to form the uteric
bud. The bud is stimulated to enter the
mesenchyme and branch to form collecting ducts.
Polypeptide growth factors are secreted by the
mesenchyme and activate the growth of the uteric
bud. Step 2 the developing bud stimulates the
mesenchyme to form the nephrons (gt 1 million /
kidney in humans). The mechanism of induction is
unclear. E-cadherin increases, allowing cells to
adhere. Increased expression of laminin and
collagen IV.
25
Kidney development recapitulates ancestral
structures
The more evolved vertebrates, such as mammals,
develop the pronephric and mesonephric kidneys
before they finally develop and maintain the
metanephric kidneys. Recapitulation it is
easier for nature to modify an existing set of
developmental instructions than to create a
totally new plan.
Practical advantage the pronephros and
mesonephros have connections to the coelom and
they function well at very low blood pressure.
They are useful for elimination of waste prior to
the development of the fully differentiated
kidney which uses higher blood pressure. Used to
form other tissues Part of the mesonephros is
used for the male reproductive system
(epididymis). The parallel tube, the Mullerian
duct, also contributes to the female reproductive
tract.
26
Lateral plate mesoderm divides to form the coelom
The lateral plate mesoderm occupies the most
lateral position. It divides to form two
layers. Somatic layer develops in association
with ectoderm. It forms the body wall and
limbs. Visceral layer develops in association
with endoderm. It forms the cardiovascular system
(including heart), and smooth muscles that
surround the gut, blood vessels, and internal
organs. Embryonic coelom the space between
these layers forms the body cavity. In the adult,
this cavity is subdivided to form the pleural,
pericardial, and peritoneal cavities.
27
The cardiovascular system develops from
mesenchymal precursors
The heart rudiment is formed early in
embryogenesis. It starts beating by the 23rd day
of development in humans. Two principle
mechanisms contribute to development of the blood
and vessels 1. Vasculogenesis generation of
the earliest small blood vessels. Mesenchyme
forms the blood cells and the endothelial cells
of vessels. 2. Angiogenesis occurs at a later
stage of development. The existing blood vessels
are induced to sprout branches into adjacent
tissue. What is the signal for angiogenesis or
vasculogenesis?
28
VEGF and Flk-I mediate angiogenesis
Vascular endothelial growth factor (VEGF)
stimulates both proliferation of angioblasts and
differentiation into endothelial cells that form
blood vessels. If VEGF is knocked out
angiogenesis and vasculogenesis fail. Flk-1 is a
receptor for VEGF that is present in angioblasts.
Mice that lack this receptor fail to form blood
vessels and they die. During development, VEGF
is expressed by hypochord (just below notochord)
and FLK-1 is expressed on cells of lateral plate
mesoderm. Mesoderm cells migrate toward the
highest concentration of VEGF and they form the
dorsal aorta.
VEGF
Flk-1
Flk-1
29
Development of the heart
Recapitulation in heart development heart
formation in humans and higher vertebrates
recapitulates early stages of development in
fish. The heart develops from bilateral
rudiments in the visceral layer of mesoderm.
These rudiments fuse to form a primitive heart
tube. Endocardium the inner layer is continuous
with the endothelium of blood vessels. Cardiac
jelly a thick layer of extracellular matrix
surrounding the endocardium. It facilitates cell
movement as the endocardium develops. Myocardium
visceral mesoderm forms the heart muscle.
30
The embryonic heart tube is divided into 4
chambers sinus venosus, atrium, ventricle, and
truncus arteriosus. This primitive arrangement is
the final form in many fishes. Early human
embryos look almost identical.
The embryonic heart tube undergoes dramatic
changes in mammals. The interatrial and
interventricular septa arise. The
atrioventricular connection is remodeled so that
2 valves form. The truncus arteriosus splits to
form the aorta and the pulmonary artery.
Splitting is accomplished by forming ridges of
tissue that grow together in each tube.
31
Extraembryonic membranes
Fish and amphibian embryos develop in water which
provides several advantages a source of food,
protection against trauma, dessication, and a
reservoir for excreted waste. Reptiles, birds,
and mammals lay eggs on land and have developed
extraembryonic membranes to assist with these
developmental processes. There are 4 membranes
amnion and chorion develop from somatopleure, a
bilayer of ectoderm and somatic mesoderm. The
allantois and yolk sac are from splanchnopleure,
a bilayer of endoderm and visceral mesoderm.
32
What are somatopleure and splanchnopleure?
Somatopleure
splanchnopleure
33
How do the membranes function in reptiles and
birds?
Amnion a sac filled with fluid allows the embryo
to float , shock absorber Chorion the chorion
and allantoic membranes form blood vessels that
enable gas exchange with the embryo, embryonic
lung Allantois also forms a reservoir for
metabolic wastes, embryonic kidney Yolk sac
forms blood vessels to carry nutrients from the
yolk to the embryo proper, embryonic digestive
system
34
What happens to these membranes in mammals?
The same membranes form in mammals, however, the
functions are further modified. Mammals develop
in the uterus rather than an egg. Amnion
continues to surround and protect the
embryo. Chorion forms the cytotrophoblast that
makes chorionic villi and forms the fetal portion
of the placenta. Yolk sac this is formed even
though there is no yolk. It will become the site
for germ cell formation (sperm and eggs). An
example of recapitulation.
35
The human placenta
As pregnancy advances, the majority of the
chorionic villi disappear while the villi near
the connecting stalk grow much larger and form
branches to achor the placenta into the
endometrial wall. Blood from the uterine
arteries is released into lacunae, large spaces
where the fetal vessels and maternal blood
interact. The placenta mediates exchange of
nutrients, oxygen, hormones, and waste products
during pregnancy.