One of the key concepts to understanding how a single celled organism can develop into a differentiated multicellular organism is to understand the central dogma. The central dogma is a term that describes how cells use DNA to produce mRNA to produce proteins. To produce a particular protein, the gene must be turned on and transcribed into mRNA, which then must be translated into protein. It is also important to distinguish between genotype and phenotype. The genotype of an organism is the genetic information (genes) it acquired from its parents. The phenotype describes how the organism appears physically, including its internal structure, and the biochemistry of its cell(s). The dynamic relationship between the genotype and phenotype is what attributes to the development of specialized and different cells. For example, consider why one of your liver cell looks different, and functions different from one of your heart cells. If the DNA in these cells is the same, how is it possible that they look and function differently?
The answer to this question is regulation. Although this liver and heart cell contain the same exact DNA sequence, not all of the genes in the DNA are turned on and producing the same exact proteins. What a cell can do is largely determined by what proteins it contains. In order to "turn on" a gene, a combination of steps must happen, which may include the binding of a specialized gene-regulatory protein to the control regions of the DNA. Both transcription and translation are regulated by multiple other mechanisms as well. For example, some mRNA may get degraded before it has a chance to be translated (preventing the protein from being produced.) Another example is called RNA Processing. After the gene is transcribed to RNA, the RNA may be cut and spliced in different ways to give rise to many different mRNAs (and proteins, all from the same gene). Alternatively, the proteins produced can be modified after translation as well (called post-translational modifications) before they become active proteins. One last mechanism is a category of genes that produces microRNAs. These are little RNA fragments that prevent the translation of specific mRNAs.
Together, all of these mechanisms mean that one gene can produce a multitude of functionally different proteins. So although the liver cell and the heart cell have the same DNA sequence, this does not necessarily mean they will be producing the exact same proteins. By controlling which proteins are made in the cell, the genes (DNA) can control the properties and behaviors of the cells, which determine the course of development. Genes control the development of the organism by determining where and when proteins are made (there are many genes involved in this process). The interactions between proteins and genes and between proteins and proteins also contribute to the properties of the cell.
One of these properties is cell-cell interactions, which is the ability of a cell to communicate with, and respond to, the cells around it. Their response to signals for cell movement, or change in cell shape brings about morphological (physical) changes in the developing organism. The cell-cell interactions are what determine how the organism develops (where the heart goes in relationship to the liver, arm, etc.) so therefore no developmental processes can be due to the function of a single gene or protein. Aside from just a single cell influencing the actions of another single cell, this can also happen in groups. One group of cells can influence the development of an adjacent group of cells. This signal can be sent through many cells, or be localized to a few cells.
Overall, the differences between cells must be generated by differences in gene activity which would lead to the production of different proteins. This leads to differences in cell properties and functions. Different proteins located on the outside of the cell, or being released from the cell provide a mechanism for cell-cell interactions/ or communication between cells. Responses to these signals can bring about physical changes in the developing organism, thus producing two cells with different physical properties and functions, but that still contain the same exact DNA sequence.
February 2013 Archives
While investigating how cells became different from one another during development, two ideas were originally proposed. One of these was called Mosaicism and the other Regulation. Mosaicism is a model of development proposed by Weismann in the 1880's, where the adult is mapped out on the embryo by a pattern of nuclear determinants. It suggested that the nucleus of the zygote contained a number of special factors, and when the fertilized egg underwent rapid cell division these special factors (determinates) were distributed unevenly to the daughter cells. The uneven distribution is what determined the fate of each cell. Initial support for the Mosaic model came from experiments performed by Wilhelm Roux on frog embryos. During the first cleavage of a fertilized egg, he used a hot needle to destroy one of the two cells, and what he found was that the remaining cell developed into a half-larva which supports the mosaic mechanism.
However, Hans Driesch repeated a similar experiment on sea urchin eggs and found a completely different result. After separating the cells at the two-cell stage he found they developed into two normal larvas that were just smaller. This lead to the other proposed model termed Regulation. This refers to the ability of the embryo to develop normally even if there are parts that have been removed or rearranged suggesting that the early embryo is unspecified and that all cells are equivalent and contain the same cytoplasmic factors. A key factor that differentiates between the experiments done by Driesch and Roux were that during Roux's experiment he left the killed cell attached. The embryo didn't "know" the other cell was dead; it still developed a functional dorsal organizer, and developed as if the other cell was still there. If the dead cell at the two cell stage had been removed, it would have resulted in whole, but small embryos.
Notes From The first part of Chapter 1 from "Principles of Development" by Lewis Wolpert and Cheryll Tickle:
Developmental Biology Notes
I. Big Question: how does a single-cell (fertilized egg) become a multi-cellular organism?
a. Which genes are express- when? Where?
b. How do cells communicate?
c. How is developmental fate determined?
d. How do cells proliferate/differentiate?
e. How are big changes in body shape made?
II. Important Definitions
a. Stem cells- ability to proliferate and develop in to different tissues
b. Cancer cells- ability to divide indefinitely
c. Embryogenesis- fertilized egg to embryo
d. Morphogenesis- development of form
i. Animal pole- pigmented upper surface of unfertilized egg
ii. Vegetal pole- lower region with accumulation of yolk granules.
iii. Cleavage- mitotic divisions where cells do not grow between each division, cells become smaller
iv. Blastula- after 12 divisions
v. Germ layers
1. Animal region gives rise to ectoderm (skin/nervous system)
2. Mesoderm, Endoderm: internal organs
vi. Gastrulation: endoderm & mesoderm move inside, body plan established
III. Origins of Developmental Biology
a. Germ cells vs. somatic cells
b. Fertilization results in the zygote
c. Meiosis produces germ cells
d. Mitosis produces somatic cells
IV. Two main types of development propsed
a. Weismann- "determinants" distributed unequally to daughter cells and so would control the cells' future development- "Mosaic mechanisms"
b. Driesch- "regulation" ability of an embryo to restore normal development even though some proportions removed/altered early in dev.
V. Cell Communication
a. Induction- one cell/tissue directs the development of another neighboring cell/tissue
b. Blastopore- slit-like invagination formed with gastrulation begins
c. Spemann-Mangold Organizer