Feb 11, 2005; Biology 2005 Albert Harris
Embryonic InductionWhen a signal from one group of cells causes another group of cells to differentiate into a different cell type than it otherwise would have.Hans Spemann, got the Nobel Prize for Medicine because one of his graduate students, Hildegard Prosholdt (Mangold) discovered that amphibian notochord mesoderm can induce somatic (i.e. skin) ectoderm above it to form a neural tube. In fact, this "chordamesoderm" induced surrounding tissues to differentiate so as to form an entire second "Siamese twin" embryo. The inference is that the reason the normal neural tube forms where it does is because it is induced by signals from the notochord
Hundreds, maybe 1000s, of embryologists focused their research careers toward discovering the chemical nature of this signal Let's all hope the true neural inducer doesn't turn out to be the Sonic Hedgehog protein. Many other examples of embryonic induction have been discovered, and for some the signal is known.
Question) How do elevators work? Answer) Elevators work by buttons! Question) Buttons make the elevator move? Answer) The button sends information that tells the elevator what floor of the building to go to. Question) Don't there have to be cables and motors? Answer) I have never seen any cables or motors, or hydraulic pistons, or anything like that; and I have ridden on thousands of elevators. Question) Buttons are strong enough to lift people? Answer) Even if these so called "motors" did sometimes exist, they are not as fundamental as the buttons, because the buttons provide the information where the elevator should go, and any "motor" would just be following orders. Question) How does gastrulation work? Answer) Wnt proteins.
The embryonic development of the vertebrate eye includes many interesting examples of induction. From each side of the brain fold out bulges "the optic vesicles,"
Where these contact the somatic ectoderm,
(that would otherwise differentiate into epidermis,, = the outer layer of the skin)
it instead differentiates into the lens, of the eye,
and folds inward to form a hollow epithelial ball. The part of each optical vesicle that touches the somatic ectoderm is induced to differentiate as the neural retina, of the eye.
Experiments have been done in which impermeable barriers (pieces of plastic etc.) were put between the optic vesicles & the skin
(prevented signalling) Then all optic vesicle cells differentiate into pigmented retinal epithelium,. Lenses can be induced from other parts of the somatic ectoderm at by grafting optic vesicles under what would normally become skin. The somatic ectoderm over the lens is induced by the lens to differentiate into ,cornea, (and become transparent, among other changes)
There are many examples in which epithelial cells and mesenchymal cells induce changes in each other's differentiation.
Programmed cell death, was given the name "apoptosis," ~1982, but had been studied by embryologists since the 1930s or before. Studies using the nematode C. elegans led to the discovery that apoptosis results from internal self-digestion by caspase enzymes. The key advantage was that nematodes only have one caspase, but mammals have a dozen or more different caspases. Several different signalling pathways can activate these enzymes
This is not the same as ordinary cell death (="necrosis")
Tadpole tail resorbtion is a classic example of programmed cell death 131 cells of a normal C. elegans embryo undergo apoptosis. Many nerve cells are removed by apoptosis (more than 50%!); & many other examples * <95% of lymphocytes undergo apoptosis, which supports the theory this is how anti-self lymphocytes are "weeded out".
Cancer chemotherapy, drugs often (always?) work by inducing apoptosis in a higher % of cancer cells than normal cells. Death of heart cells during heart attacks, and death of brain cells during stroke may be ~90% apoptotic, although set off by lack of enough oxygen. A quick-acting anti-apoptosis drug might prevent as much 9/10s of the tissue death from occurring.
A human protein, named bcl-2, localized in mitochondria,
inhibits apoptosis. The subclass of Non-Hodgkins' Lymphoma called follicular lymphoma , is a cancer of B-lymphocytes; Many other kinds of lymphoma are caused by other chromosome "translocations" that put promoters for antibody proteins just upstream of genes that stimulate cell growth and/or division.
Questions to think about:1) Why do chromosomes tend to break so often just downstream of the promoters for antibody genes?2) When such breaks rejoin with breaks on other chromosomes, cancer will be the result if what sorts of genes need to be located on the downstream side of the joining site? Why? 3) Why do such cancers occur only in cells that differentiate as lymphocytes? 4) If follicular lymphoma is caused by too much bcl-2 protein, so that the cancer cells accumulate, even though their growth rates are not abnormal, then why is this cancer treated with drugs designed to kill fast-growing cells? 5) Would you expect this treatment to cure anyone? 6) What would you conclude if this treatment sometimes cured people, even though based on completely false assumptions about how the drugs killed cancer cells, and also about the cause of this form of cancer. Can two wrongs make a right? What about 3 lefts? Pasteur believed in completely false theories about what causes immunity, & invented his vaccines on the basis of those false theories
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