Unsolved Problems Related to Embryology: Oct. 6, 2017

"Cytodifferentiation" = Differentiation. Examples: becoming a liver cell, cardiac muscle cell, macrophage, B-lymphocyte, T-lymphocyte, Granulocyte, Rod cell, Cone cell, Oligodendrocyte, Schwann cell, etc.

More than a hundred differentiated cell types in humans and other mammals
(Somewhat arbitrary which consider different: Red sensitive cone cells, vs green vs blue sensitive)

"Stem cells" which used to be called "Archeocytes" are undifferentiated and/or able to become any of several differentiated cell types (maybe any or all differentiated cell types).

"Luxury genes" (only in differentiated cells) as compared with "Housekeeping genes" (in all cell types)

Being differentiated is usually self-perpetuating (seldom reversible). Plant cell differentiation is more changeable. The mechanism of self-perpetuation is not yet known. You might discover how it works.

If you fuse a mouse liver cell with a chicken liver cell, the "heterokaryon" will continue to transcribe the liver luxury genes for both species. But if you fuse either a mouse or a chicken liver cell with either a mouse or chick heart muscle cell, then both sets of luxury genes "will be turned off" (will stop transcription); as if both differentiated states turned each other off.

Thought question: Imagine discovering a method that caused anti-myelin multiple sclerosis cells to fuse with any other differentiated cell type. Or maybe that causes anti-myelin B cells to fuse with anti-myelin T lymphocytes.

Two exceptions to this rule about "turning off" each other's luxury genes:

Bird red blood cells have nuclei, but these are very shrunken and don't transcribe.
Fusing a chicken red blood cell with a mouse heart muscle cell will result in the chicken nucleus swelling and transcribing bird heart muscle genes and making heart muscle proteins. How could you explain this?
Does it tell you anything about mechanisms that control gene expression.

Fusing chicken liver cells with (multinucleate) skeletal muscle cells will result in the liver cells switching cell types, and transcribing chicken voluntary muscle cells. Please suggest a molecular explanation.

Suppose all the luxury genes of each differentiated cell type had promoter regions with the same base sequence. Why might you expect that? As the basis for controlling differentiation? How could such a pattern be detected?

Does anatomy consist of the spatial arrangement of differentiated cells? If you control which cell type differentiates at each position in the body, would that be sufficient to create anatomy?

At all the locations where bones are to form, whatever cells are located there get stimulated to transcribe the subset of genes that will cause cells to differentiate into osteoblasts. Is that how bone shapes and locations are caused?

Alternatively, do bones develop with the shapes and at the locations where cartilages had differentiated & grown?

Skeletal muscle cells differentiate only from cells originally located in 2 stripes along the back. From that original location, some force pushes or pulls them to the places where the gastrocnemius, biceps, triceps, and the other 600+ voluntary muscles will form.

Salamanders, especially newts, can regenerate legs, tails and several other organs.
Frog tadpoles can also regenerate their legs, if they are cut off soon after they first form;
But then they gradually lose the ability to regenerate. Try to invent causal explanations.

When salamander muscle cells are radioactively labeled, then if a leg is cut off, all the new muscles that develop result from rearrangement of cells that had been parts of muscles previously located near the cut edge. .

The skeletons of regenerated limbs are 90% made of rearranged skeletal cells located near the cut edge. .

What do you conclude from those observations about the mechanism of leg regeneration?
Is it a repeat of the process that originally formed the legs? Or is a different mechanism required?

Is regeneration a process of geometric control of the positions where undifferentiated stem cells will change into muscle cells, skeletal cells, nerve axons, blood vessels, etc. (Is that what most people assume?) Is limb regeneration the result of minimization of the free energy of the muscle cells, skin cells, etc.

Do legs regenerate by geometric rearrangements of cells that had already been differentiated into muscles, skeleton, etc. before the amputation?