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"…the gametes are the only cells in the body that can generate an entire new organism…[Germ cells] are the means by which species form and change in evolution."
-- Chris Wylie (1)

The adult human body is made up of billions of cells. Most of these cells are working to keep a single individual alive and healthy, but a small percentage of cells are working for many future generations. The average American has 2-3 children. That means only 2-3 cells will contribute to the next generation, and these 2-3 cells (germ cells) must contain the potential to become a whole new organism. Therefore, these cells must be selected early and separated from other cells so they are not subject to differentiation and specialization stages that would restrict their potential. Long before a woman even realizes she is pregnant, the developing embryo inside her has already specified which cells will make her grandchildren. This article will first address how these cells are singled out, then mention how these cells may be maintaining the ability to generate whole organisms.

GERM CELL SPECIFICATION

Research today has uncovered a long list of genes involved in germ cell specification. Many similarities have been found between vertebrates and invertebrates. Soon after fertilization of an egg, the cell nuclei fuse and the cell begins a series of rapid divisions. Most animals produce a molecular "tag" of sorts to mark cells that will become germline. In the nematode C. elegans, for example, a specific protein floating in the cell cytoplasm is segregated so that some cells receive all of that protein and other cells have none. With each division, the protein is segregated into a smaller and smaller subset of cells. Only those cells containing that protein have the potential to become germ cells (1, 2). Most animals use a similar technique to identify and biochemically separate potential germ cells (2,3). Often, potential germ cells will be physically separated from other cells as well. For example, in the fruit fly Drosophila melanogaster, most cells divide rapidly without cytokinesis, forming a large mass of free-floating nuclei. Germ cells, however, maintain their cell membranes and cluster themselves at the bottom of the embryo. They are the only cells with membranes until rapid division has ceased.

At a certain point in development, called the mid-blastula transition, the embryo has used up all the proteins and mRNAs supplied by its mother. Cell divisions slow down as the cells start producing their own nutrients and building supplies. Soon after this, cells start migrating to form three basic cell layers: ectoderm, mesoderm, and endoderm. At this point, germ cells migrate into the center of the embryo and start to multiply. Much later, when organs have been formed and most cells have become highly specialized, the germ cells remain essentially unchanged. They maintain their totipotency, or the ability to become any cell type (1,2).

Maintaining totipotency is a hot topic in scientific research. If we can learn what makes a cell totipotent, perhaps we could regenerate damaged organs or develop treatments for some forms of sterility. Scientists have observed one slight difference in gene transcription between germ cells and other embryonic cells. When most cells stop depending on maternal stores, and start actively transcribing their own genes, germ cells do not. Germ cells remain transcriptionally inactive 3-6 stages longer (exact timing differs from species to species) (3). Germ cells may operate on a totally different time schedule, restricting divisions and differentiation to prolong their totipotent state. There is still much to be learned about germ cells.

Genes involved in the specification and maintenance of germ cells are currently being studied. The field of germ cell research is rapidly expanding as new molecular and genetic tools are being developed. As we learn more about the cells that create us, perhaps we will better understand the forces that cause us to change and evolve.

References:
(1) Wylie, Chris, Germ Cells, Cell 96 pp. 165-174 (1999)
(2) Gilbert, Scott F., Developmental Biology (Fifth Edition), Sinuar Associates, Inc., Sunderland, Massachusetts, 1997 (Chapters 5, 12 and 22)
(3) Saffman, E., Lasko, P., Germline Development in Vertebrates and Invertebrates, Cellular and Molecular Life Sciences 55 pp.1141-1163 (1999)