Embryology Biology 441 Spring 2010 Albert HarrisLecture Notes for March 19
![]() Embryonic artery, wrapped in collagen fibers (yellow) First sub-topic, blood vessels: which are formed from mesoderm. Capillaries; Veins; Arteries; + also Lymphatic ducts. In all of these, the innermost lining is a sheet of a special kind of epithelial cell, called "endothelial cells" "endothelium" (Don't be fooled by the name, these are NOT formed by endoderm!)
Capillaries are narrow hollow tubes of endothelial cells, with little or no other reinforcement. Despite their very thin walls, the pressure in capillaries is more than in veins, and in many capillaries the pressure is almost as strong as in arteries!!?
But earlier in the course you learned about P = C*T + c*t Veins are much wider tubes, in which the inner-most lining is a tube of endothelial cells, but they are surrounded by many layers of fibroblasts (mesenchymal cells), and wrapped by Type I collagen fibers (which are mostly secreted by the fibroblasts).
Arteries: innermost layer of endothelial cells
Elastin is rubber-like, 'stretchy'; In contrast to collagen which forms strong nylon-like fibers and sheets. The aorta differs from other arteries in that its walls have many fewer smooth muscle cells, and many more fibroblasts, and LOTs more elastin, along with the collagen fibers. Here is a photograph I took of a cross section through a vein and an artery. (a normal artery)
The artery is in the upper-middle. One of the biggest causes of human death and disability is the disease "atherosclerosis". It is true that if the concentration of cholesterol in your blood is high, then you are more likely to have your arteries blocked by atherosclerotic "plaque".
A cross section of a human artery blocked by atherosclerosis.
It is definitely NOT true that cholesterol sticks to the inside of anyone's arteries. Clotted blood & blood platelets do stick there, and cholesterol accumulates in or among the cells that are blocking the artery.
WHAT IS THE TRUE STORY: * Among all those extra smooth muscle cells, that are bulging into the space where the blood should flow, cholesterol does accumulate. So there is some kind of connection. But many of you will be going into medicine or medical research, so you should be told the truth, not Aesop's fables, and in this case the truth is that nobody really understands what's happening. One theory: The blockages are tumors of the smooth muscle cells, analogous to many small cancers, caused by somatic mutations. Another theory: Turbulence in the blood stimulates blood platelets to secrete PDGF (Platelet-Derived Growth Factor), a protein which is known to stimulate smooth muscle cells to grow and divide and also is a chemotactic attractant for them. Notice that neither of these theories predicts the (true) fact that these over-growths of smooth muscle cells are larger and worse in animals and people who have more cholesterol in their blood. If you could invent some possible reasons, and also how to test them, then that would be a HUGE contribution to medical science. Research science is full of riddles and paradoxes of this kind.
Usually you can't just observe complex phenomena. Inventing theories tells you what details to be curious about!
The following are entirely imaginary; there is no evidence for them. (yet)
2) Cholesterol deposits make smooth muscle cells more sensitive to PDGF. 3) Cholesterol stimulates platelets to secrete more PDGF, and it's just a coincidence that cholesterol also gets deposited in among the extra smooth muscle cells. 4) Cholesterol deposits prevents apoptosis of extra smooth muscle cells, so that excess accumulations of smooth muscle are not eliminated.. 5) Cholesterol somehow causes or allows smooth muscle cells to pull more strongly on collagen fibers, or elastin fibers, or to contract more strongly. 6) Cholesterol deposits between smooth muscle somehow stimulates them to divide. 7) 8) 9) 10) please invent more theories!!!
Most of these are in the yolk sac, in birds and mammals. Maybe that's why mammal embryos continue to have yolk sacs?
Red blood cells and white blood cells differentiate inside; The yolk sac is one of several different organs that are used as locations for the hemopoietic stem cells which form red blood cells (and also white blood cells). These stem cells move to the liver, and later to the bone marrow. Embryonic and fetal hemoglobins are different from (and coded for by different genes than) the hemoglobin we have in the red blood cells we make after birth. Fetal hemoglobin binds oxygen slightly more strongly than adult hemoglobin, which increases the amount of oxygen that is transferred across the placenta from the blood of a pregnant woman to the blood of the fetus developing inside her. Two other interesting aspects are: #1) The genes for embryonic and fetal hemoglobin proteins are directly adjacent to the genes for adult hemoglobins, with the early blood cells activating one gene, and then later blood cells activating the gene next to that one. The mechanism isn't known, nor whether there is any similarity to the mechanisms that cause adjacent Hox genes to be transcribed in adjacent tissues. #2) A few people continue to make fetal hemoglobin all their life, instead of switching to the adult hemoglobin genes, and the symptoms of this are almost unnoticeable! So far as I know, it hasn't yet been discovered what mechanism causes this; but it could become a new and better treatment for sickle-cell anemia (and other genetic defects of adult hemoglobins), if you could discover a drug or other treatment that switches their hemopoietic stem cells back to transcribing the genes for fetal hemoglobin.
The Skeleton: formed by mesodermal cells,
except the face, where skeleton is neural crest cells Vertebrate skeletons are made partly of bone and partly cartilage. Bone compared with Cartilage
Bone is stronger and more rigid,
Cartilage is lighter, flexible, weaker,
Bone is a tightly woven composite of 1/3 type I collagen fibers,
embedded among crystals of calcium phosphate (2/3rds by weight)
(& also fluoride and hydroxide) (dentine is almost the same)
Bone is made (but not really secreted!) by osteocytes. (= osteoblasts)
Deposition of bone is called "ossification".
Another special differentiated cell type (osteoclasts) constantly dissolves and destroys bones. Bone is a very dynamic tissue, being constantly
destroyed and remade. When osteocytes don't keep up with the osteoclasts
the result is osteoporosis. There are many unsolved problems here. Many drugs are designed to strengthen the calcium salts, but these drugs can have very painful and harmful side effects (do a web search and read the horrifying reports from patients). A possible explanation is that these "bone strengthening" drugs induce programmed cell death (apoptosis) in the osteoclasts (bone digesting cells) and also some or many other cell types such as in the digestive tract.
Cartilage is a mixture of type II collagen and chains of sugar molecules that have sulfate groups covalently bound to them. The sulfates ionize,
and their negative charges keep a cloud of cations (like Na+) nearby. Cartilages grow partly by increased synthesis of sulfated sugars, and partly by selective weakening of both the internal and surface collagen.
As an analogy, imagine controlling the shape of a balloon partly by forming more gas inside, and partly by weakening the rubber.
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Elastic cartilage of ear | Elastic cartilage seen by polarization microscopy |
The support of your ears and tip of your nose are elastic cartilage, which is more flexible than hyaline cartilage which constitutes most of the rest of the cartilage.
Hyaline cartilage by polarization microscopy
In polarization microscopy of tissues, the colors show you where collagen fibers (or other fibers) are lined up in a particular direction. Fibers in one direction produce the color blue, and fibers oriented perpendicular to them produce complementary colors, like red and yellow. There has to be a net majority of fibers in a certain direction to produce either color, because the effects cancel each other out. Nevertheless, some parts of embryonic development can look like a 4th of July fireworks display when studied by these (simple and relatively inexpensive) methods.
In some vertebrates (sharks and salamanders) the skeleton is mostly made of cartilage (instead of bone). Much of this cartilage becomes calcified and can be quite stiff and strong (but weaker than bone).
The articular cartilages serve for what amounts to lubrication.
They feel and look somewhat like sheets of wet teflon.
Articular cartilage, and bone at right side
Notice the directional orientation of the cells
Bone formation = ossification.
During embryonic development of mammals and birds (including humans), nearly all the "bones" start out being made of cartilage!
Chicken leg skeleton at a stage at which it is all cartilage
In other words, when you were an embryo, your femur, pelvis, radius, ulna, etc. were all made out of cartilage instead of bone! Only certain skull bones, especially the flat ones, are made out of bone from the very beginning. Later, during development, little-by-little, and continuing up to about age 20, this cartilage is dissolved and replaced by bone. NOTE: the cartilage isn't changed into bone; the cartilage is replaced by bone.
Polarized light view of a chicken leg cartilage begining to ossify
The bone appears yellow
The two blue lines are collagen
Replacement of cartilage by bone used to be considered as a recapitulation (in the sense proposed by Ernst Haeckel).
He believed that our distant ancestors evolved cartilage first,
and then millions of years later our less-distant ancestors evolved
bone; and he believed that embryos are (for some reason!) obligated
to repeat such evolutionary sequences. This concept dominated embryology
for about 50 years, but has been considered misguided for many more years
than that.
Now it is believed that bone evolved before cartilage, and that replacement is a means of allowing growth.
Bones that undergo this process are called "replacement bones";
A synonymous term is "endochondral bone".
The term "dermal bone" refers to those (skull roof, etc.) bones that are made of bone from the start.
The last parts to ossify are the epiphysial plates;
when they ossify, the bone can't grow any longer.
(Rabbits, chickens, etc. just have an epiphysis instead of a plate)
Cross section of rabbit epiphysis seen by polarization microscopy
Up to around 20-21, the age of a skeleton at death can be dated within +/- a few months by noticing which epiphysial plates had "closed" and which ones had not. Ossification is very stereotyped.
Mutations in certain genes can cause premature ossification "closure" of epiphysial plates. Basset hounds and dachshunds have short legs because of this type of mutation; also some breeds of sheep.
So-called "chondroplastic dwarfism" in humans results from an equivalent (dominant!) mutation.
(no one knows what protein these genes normally code for: an enzyme?)
During the healing of broken bones, bone around the break is dissolved, cartilage is formed in its place, and then this cartilage is gradually replaced by bone, as occurred during development!
Gonads themselves are formed from the same tissue in both sexes:
Testis (testes plural) in males and ovaries in females.
They are both formed from thickenings in the wall of the coelomic cavity, which makes then lateral plate mesoderm.
These thickenings are called genital ridges.
The actual future sperm and egg cells do NOT develop from cells of the genital ridge. Sperm and egg cells develop from special cells called "primordial germ cells", that migrate to the genital ridges from some other part of the body
The places from which the primordial germ cells start out differs widely between different kinds of animals.
In mammals, PGCs originate in the yolk sac.
In birds PGCs originate from a crescent shaped region of the zona pellucida in front of where the body forms
In flies and nematodes PGCs come from special cells at the extreme posterior end.
There may or may not be any kinds of animals in which the future egg & sperm start out located in the same place as the gonads.
(& please tell me if you hear of any.)
If you kill or remove the PGCs from an embryo, or keep them from getting to the genital ridges, that animal will be sterile.
Grafts of chicken primordial germ cells from one egg to another will result in animals that produce eggs or sperm that have different genes than the parent.
One of the world leaders of research on primordial germ cells is out at the NIEHS in the Res. Triangle Park, and one year a student in this course did research with him, and we had PGCs crawling around in dishes. We were trying to prove whether or not they were guided by chemotaxis, but we didn't succeed.