Lecture notes for Friday, January 18, 2013
The body is made out of about 250 differentiated cell types.
Ten examples:
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1) Pigmented retina cells are one cell type [they are derived from neural tube ectoderm]
2) Pigmented cells of the skin are another cell type [neural crest ectoderm]
3) Epidermal cells of the skin are several cell types [somatic ectoderm]
(the sweat gland cells, several cell types in each hair) [All derived from somatic ectoderm]
4) Skeletal muscle cells are one cell type [derived from somites of mesoderm]
5) Cardiac muscle cells are one cell type [from lateral plate mesoderm]
6) Smooth muscle cells should be categorized as two, or more, cell types. [mesodermal]
7) Thyroid gland cells are one cell type [endoderm]
8) Liver cells are one (or more) cell types [endoderm]
9) The beta cells of the pancreas are one differentiated cell type. [endoderm]
10) Sperm cells and oocytes are each one differentiated cell types
(but are considered not to be part of any of the 3 germ layers)
Decisions arise, such as whether to call the blue sensitive, green sensitive and red sensitive cone cells of the retina as being three different cell types.
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Each differentiated cell type is the way it is because of which genes are transcribed.
Nobody has made a list of the compete set of genes that are selectively transcribed in each differentiated cell type. The genomics people ought to be trying that. I don't know how far along they are; it is a worthy goal.
Sponges have at least 3, and maybe 10 differentiated cell types.
Hydra has at least 3, and probably 5 or more.
All vertebrates have about the same number (~ 250) of differentiated cell types.
Plants also have many kinds of differentiated cells. Enough is known about plant development to fill an entire semester course; in graduate school I took such a course, and there was plenty to learn. (Ian Sussex and Arthur Galston taught it; and it was fascinating.)
Differentiated cells of plants can (often) be stimulated to switch from being on cell type to being another cell type. For example, you can stimulate root cells to differentiate from what had been stem cells. That's how you grow whole plants from cuttings. Whole plants have been grown from plant tissue culture cells, since the 1950s. To help prevent extinction of Venus Fly Trap plants, tissue cultures have been made, and then stimulated to form thousands of whole plants, each from a cluster of cells. Certain chemicals (auxin is an example) stimulate differentiation into different plant organs. (auxin stimulated differentiation of root cells)
Animal cell differentiation is (almost) irreversible.
Rare examples of real dedifferentiation, and dedifferentiation as a another cell type.
Some very strong self-perpetuation mechanism locks cell permanently into remaining the same.
The molecular mechanism of permanence has not yet been discovered;
There are no good theories about how it works.
There is very little research trying to discover the mechanism that keeps animal cells "locked"
into their particular one of the 250 cell types.
It isn't even known what mechanism simultaneously turns on each of the 250 sets of genes, each of which is expressed in one cell type.
These sets of genes overlap.
Thousands of genes are expressed in ALL differentiated cell types.
e.g. genes for metabolic enzymes.
Also genes for microtubules, actin, myosin (if which there are different kinds.
They are called "Housekeeping genes"
Genes that are only expressed in one or some differentiated cells are called "Luxury genes"
Some Luxury genes are only transcribed (and the proteins made) in ONE cell type
The Hemoglobins are a good example.
The red-sensitive, blue sensitive and green sensitive light detecting proteins
in Rod Cells in the retina are three more examples.
Some Luxury genes are only transcribed (and the proteins made) in TWO cell types
The genes for the enzyme that are a good example that synthesize melanin are a good example.
(Pigmented retina cells and pigmented cells of the skin are example.
There are no good theories about how this works. Try to think of one yourself!
A contest for the best: submit enries:
TWENTY DOLLAR PRIZE FOR THE BEST THEORY TO BE SUBMITTED NEXT FRIDAY
Theories can be tested either by e-mail or printed out, or hand written.
(Or I will buy you your choice of a serious biology book in the Bulls Head Bookshop.)
[This contest will only take place if I get at least 10 serious theories submitted]
Some unknown mechanism absolutely prevents cells from differentiation in 2 cell types. or even transcribing one luxury gene that is normally only transcribed in another cell type.
e.g. Turn on transcription of hemoglobin genes in pigmented retina cells ,
make pigment in a nerve cell, etc, etc
Nobody knows the mechanism of this, either.
I will consider having another 20$ or a Bull's Head Book for the best theory on this, too,
if students want to, and submit a reasonable number (like at least 10) different theories.
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Notice how genomics solves certain questions.
But ignores many of the most important conceptual problems
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Each of the 250 cell types is reached by a branching pattern, like a series of railway switches.
The first 3 branches are the ectoderm, mesoderm, & endoderm. (also "germ cells")
The mesoderm then branches into sub-branches, which you have learned.
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1) Notochord
2) Somites
3) Intermediate Mesoderm
4) Lateral Plate Mesoderm
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1) Skeletal muscle
2) Skeleton Which branches into two: cartilage & bone
3) Dermis (inner layer of skin)
What is the molecular mechanism of this branching pattern?
[Should we have another 20$-or-a-serious book for-the-best-explanatory theory?]
(The same branching pattern is conserved during evolution, i.e. same branching pattern in humans, as in fish, as in frogs.
(Even in insects, clams, flatworms, the branching pattern is almost the same.)
About Nematodes, we should discuss how similar the branching pattern is!
Why is this same branching pattern conserved?
[Another 20$-or-a-serious book for-the-best-explanatory theory???]
An early theory was that very primitive organisms only had two or three differentiated cell types.
The words ectoderm and endoderm were invented as names for the hypothetical first two differentiated cell types
Another good contest question is this: << Why are the branches almost always accompanied by epithelial folds or other geometric rearrangements of cells?
Is this cause, or is this effect? Can folding cause division into brain and skin?
Can another fold cause the retina to divide into pigmented retina versus neural retina?
Or a major fold in the brain be the switch between sensory versus motor nerves?
TOPICS FOR ANOTHER BOOK/$20 CONTEST FOR THE BEST THEORY?
TWO QUESTIONS:
#1) Why/how does cell rearrangement cause branching in differentiation; Or does it? (Which is cause and which is effect)
#2) Why can't / doesn't genomics answer these questions?
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a) Lack of interest? If so, Why?
b) Methods are not suited for questions of this kind?
c) What sort of base sequence evidence could prove one theory and disprove an alternative theory?