Embryology - Biology 104, Spring 2006 - Albert Harris and Corey Johnson

 

OUTLINE OF SIXTH LECTURE: Jan 27, 2006, by Corey Johnson

Experimental Embryology: Mosaic vs Regulative development

Hans Driesch's experiment demonstrated a concept known as regulation. As discussed (1/25), he separated sea urchin blastomeres resulting in smaller but complete sea urchin larvae.

The reverse experiment, joining two sea urchin zygotes, results in a larger, complete sea urchin.

Contrary to Roux's experiment where the live and dead blastomeres were left together, frog blastomeres that are separated at the 2-cell stage do the same thing as sea urchins (though they form frogs not urchins)

This phenomenon is known as regulation. The 'adjustment' of cells to a new position, including the gain or loss of neighboring cells, resulting in seemingly normal development. If you take your roommate's credit card and place it to the right of your computer keyboard will it become a mouse? That's how bizarre development can be.

There are limits to where and when regulation occurs. 2 blastomeres separated can fully function as if they were zygotes and produce a full embryo. On the other hand if you take a piece of the neural tube and transplant it to the skin, it remains neural. There seems to be a "stage" in a cell's lineage where restriction has produced an inability to compensate, to regulate. This appears to be dependent upon some combination of which path is taken by the cell and how far along that path it has gone.

    1. the transplanted cell might sense its neighbor's identity
      - the lack of such information might be used, too (like an isolated blastomere senses that it's alone and thinks: Hey, I must be a zygote!
      - it must have the ability to interpret and respond to neighboring cues

    2. the transplanted cell might sense its own identity
      - we might think of identity as a transcriptional profileÉ the amounts and types of RNAs/proteins found in a cell that are a unique combination-specific to one type/lineage of cell
      ? What characterizes a cartilage cell? Can we think of blastomeres in these same terms? Are they "cell types", or are they just "blastomeres"? If a cell can change/decide its fate based on where it is, maybe one of its characteristics is developmental plasticity rather than type II collagen production. Remember, this terminology helps us to understand and communicate these ideas, but don't allow it to confine your thinking.

    3. the transplanted cell must have 'access' to the machinery needed to change cell types/fates
      - Most tend to think of 'access' as being regulated by transcription factors
      ? Can you think of another way, a cell might restrict access to the machinery needed to change cell types/fates?

Embryologists have defined the following terms or stages to describe what we believe is occurring:
    1. Competence - cells are ready to receive instruction
    2. Specification - signals are received altering/instructing fate
    3. Determination - lineage is determined, unalterable
    4. Differentiation - manifestation of determination. Cell type is expressed
    (ex: cartilage expresses glycoaminoglycans)

Fate is generally seen as a flexible state, while lineage implies inflexibility... though some people incorrectly use them interchangeably

Many experimental manipulations have given insight to where and when regulation occurs in the embryo. Examples include:

    1. Defect experiments - removal, or ablation of cells physically or with lasers to examine what happens to the rest of the organism
    2. Isolation experiments - removing cells or tissues from an embryo to culture in isolation from the rest of the embryo
         a) determines if a tissue relies on another
         b) will ectoderm become neural tube if removed from the embryo? No
    3. Recombination experiments
         a) grafting a second notochord will cause ectoderm to form a second neural tube
    4. Transplantation experiments - replacing one part with another
         a) Will a leg bud form an arm if it's transplanted to where the arm bud should be? no

These manipulations are quite useful in studying regulation. Many have used these techniques to examine when and how tissues become competent, specified, and determined.

Regulation is in stark contrast to the behavior of another type of development: mosaic development. The best example we know of is Caenorhabditis elegans, the round worm (nematode). When cells are separated they don't form smaller, normal embryos. Rather they form abnormal embryos, though not usually half-embryos like Roux saw.

C. elegans have a very defined pattern of cell division resulting in cells that are already dedicated to a particular lineage. The very first cell division is asymmetrical, resulting in a large cell (AB cell) and a smaller (P1 cell). Unlike the frog egg, which can produce two frog embryos if divided, the two cells of the worm have already been determined to a particular lineage. They each give rise to their respective progeny irrespective of the presence of one another.

This is called mosaic development. This concept is quite similar to what Roux thought he had witnessed. Each part of the whole becomes progressively divided and portioned-out to the progeny, resulting in a very ordered, mosaic.

Other examples of organisms that develop this way are many mollusks and insects... though there are exceptions within these groups.

Importantly, organisms are not (or should not be) classified as regulative or mosaic developers. Even C. elegans has more recently been shown to regulate... though this is in response to specific cell ablation. Most organisms have a combination of both. So what is the fundamental difference?

Ideas from people who study these things:

    1) Regulative and Mosaic development are fundamentally different mechanisms for development
    - reciprocal signaling among cells --> Regulative - unequal distribution of cytoplasmic determinants --> Mosaic
    Ex: the development of the ascidian (tunicate: primitive chordate) involves a mystical yellow substance that is found in the zygote: the yellow crescent. As cleavage ensues, the yellow cytoplasm is restricted to the posterior of the embryo

    2) Same mechanism, but the timing is different. Early lineage decisions, Mosaic. Late lineage decisions, Regulative

    3) A third option analogous to the ability to regenerate.
    - regulative development is like the ability to regenerate, mosaic is like not being able to regenerate

What exactly did Roux observe? What was special about the dead cell that caused the development of the right half even when the left did not develop? What ever it was, was sufficient to fool the live cell all the way to neurulation... a very important observation. Are there right and left sided cytoplasmic determinants? Is that what was happening? If you could take a dead blastomere from the right side, and place it next to a zygote, would the zygote necessarily form the corresponding left side?

 

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