January 11th lecture Embryology   Biology 441   Spring 2008   Albert Harris   Basic concepts and (strange!) facts of Embryology Embryology is the study of the mechanisms by which genes cause anatomical structures (cause those structures to form, to maintain and repair themselves, and eventually to age) The textbook assumes that mechanisms of formation of anatomy are fundamentally different from mechanisms of repair, and different from mechanisms of maintenance, and that aging results from yet other kinds of mechanism. Nobody really knows, or CAN KNOW until these mechanisms have all been discovered and repaired. My own bias is that the same set of mechanisms are used for repair as for original development, because that's true in sponges and Hydra, & maybe sea squirts! DNA base sequences  ->  ->  (mysterious causal mechanisms)  -> Muscles & Bones & Nerves etc. Anatomy consists of: 1) Cell differentiation 2) Geometric arrangement of differentiated cells 3) Extracellular materials like collagen, cartilage and bone About 250 different kinds of differentiated cells (~250 differentiated cell types) in humans. A Dozen Examples of differentiated cell types: * Red blood cells are one kind of differentiated cell type * Osteocytes are another kind of differentiated cell type * Osteoclasts are yet another differentiated cell type * Liver parenchyma cells are another example of a differentiated cell type * The blue-sensitive cone cells in your retina are another example ** the red-sensitive and green-sensitive cone cells are two other examples * Sperm cells are also examples of a differentiated cell type * So are oocytes. * So are the Leydig cells that make up much of the rest of the ovary. * So are the Sertoli cells that physically and nutritionally support sperm. * B-lymphocytes are another one of the 250 differentiated cells of our bodies. (But sponges and hydras have only 5 or 10 differentiated cell types, and other kinds of animals have other numbers of differentiated cell types)> Sponge cell types include: 1)* the flagellated "choanocytes",         * Epithelium-like "pinacocytes", of which there may be 3+ sub-types 2) (pinacocytes that line the excurrent canals) 3) (pinacocytes that form the outside surface of the sponge) 4) (pinacocytes that form the bottom of the sponge, where if sticks to rocks, etc.) 5?) Porocytes, or maybe they are just surface pinacocytes behaving in a special way) 6)* Mesenchymal cells that secrete collagen 7)* Mesenchymal cells that secrete spicules (unless these also secrete collagen?) 8??) Archeocytes, that supposedly can differentiate into some or all other types? Hydra cell types include: 1) External myo-epithelial cells 2) Internal (digestive) myoepithelial cells. 3) Nerve cells 4) Cnidoblast-secreting cells (that make the stingers) and probably five or ten others I am really not an expert on Hydra (Unlike sponges, which I have actually done research on) One particular species of Nematode worm, C. elegans, was selected for intensive study, among other reasons because each individual develops EXACTLY the same number of cells in EXACTLY the same geometric arrangement. They have a certain number of nerve cells, a certain number of skin cells, etc. Except some of their mutations cause changes in these numbers. Such constancy also occurs in Rotifers and several other invertebrate phyla, and one kind of fungus. The phenomenon is called "eutely", and was discovered in the 1800s by Germans, because only they had the patience to count all 987 or 1234 cells in a given species of organism TWICE! It's the kind of thing that might have been invented by Prussians, and would be liked by them! Two of the best C. elegans researchers in the world are Professors in this department (Bob Goldstein and Shawn Ahmed) As you might guess, embryonic development in these worms occurs by exactly the same cell lineage. Organisms with very consistent cell lineages are said to have mosaic development, and in sea squirts and clams that consistency is known to be caused by special cytoplasmic materials that get distributed just into certain cells during cleavage. But it's still a mystery how this works, what the substances are, and whether this is the reason for the mosaic development of nematodes. Incidentally, the constancy of cell number (eutely) occurs only in a few of the kinds of animals with mosaic development. But I think all species with eutely MUST have mosaic development, and must have exactly consistent cell lineages. The cell lineages of clams and sea squirts are not quite so exact, and were discovered by the American, Conklin, at the Marine Biological Laboratory at Woods Hole. An Englishman named Sulston worked out the exact cell lineage for C. elegans, published it in the American journal "Developmental Biology", and received a 1/3 share of a Nobel prize for this.     Each differentiated cell type makes and contains a certain combination of a thousand or so proteins. For example, only red blood cells make hemoglobin, even though all cells have the genes that code for hemoglobin: they just don't transcribe (=make the RNA for) their hemoglobin genes, etc. Hundreds of genes are "expressed", in the sense that their proteins get made, in all or nearly all differentiated cell types. Such genes are called "housekeeping genes". Other genes get expressed in only one differentiated cell types, or only on 2 or only 3 etc. and are called "luxury genes" (because nobody knew enough Greek to invent a special term!) Whether genes are transcribed is controlled by the binding of special proteins ("transcription factors") to special non-transcribed control regions ("promoter regions")that are located a few dozen or hundred base pairs "upstream" of the gene for each protein (the "structural gene"). But I find that fewer and fewer scientists are familiar with this latter term, anymore. Some of my best friends are molecular geneticists, but my impression is that they tend to be rather ignorant. The deepest thinkers go into herpetology, or things like that. In principle, there could be a certain DNA base sequence just upstream of every one of the structural genes that gets expressed in each different differentiated cell type, and there could be one specific transcription factor whose surface charges exactly fit any DNA with that base sequence, and stimulate transcription of all genes located closely downstream from those promoters. In fact, it always seems to be more complicated, with more than one transcription factor for each differentiated cell type. It would be a great discovery to find out, for sure, exactly how cell differentiation is controlled. An aspect of differentiation that textbooks don't mention is that some mechanism prevents cells from combining two cell types. Apparently, expression of one set of luxury genes inhibits the expression of other sets of luxury genes. It is as if there were some absolute law against anyone becoming a lawyer who is also a physician, or who is also a pharmacist, and vice versa. In fact, very few MDs also become JDs, but there is no law against it, nor any other kind of mechanism to prevent it. But some very strong mechanism does prevent cells from differentiating as muscle cells and as nerve cells, at the same time. Experiments have been done in which tissue culture cells are fused with each other. When the two cells are of the same differentiated cell type, then the fused cells will continue to have their differentiated characteristics, and go on transcribing the same set of luxury protein genes. But when you fuse cells of different cell types, then both sets of differentiated characters are extinguished, immediately. There are some interesting exceptions to this rule, such as what happens if you transfer inactive nuclei without cytoplasm, or if you fuse a multinucleate cell with an individual cell of another cell type. Can you guess how and why the results differ in these cases? Certain cancer cells are the one exception that I know about, in the sense that they often express combinations of genes that are luxury genes for different cell types, such as when long cancer cells secrete protein hormones normally made in some endocrine gland.

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