Primordial Germ Cells
Development begins with fertilization, the process by which the male gamete, the sperm, and the female gamete, the oocyte, unite to give rise to a zygote. Gametes are derived from primordial germ cells (PGCs) that are formed in the epiblast during the second week and that move to the wall of the yolk sac (Fig. 2.1). During the fourth week, these cells begin to migrate from the yolk sac toward the developing gonads, where they arrive by the end of the fifth week. Mitotic divisions increase their number during their migration and also when they arrive in the gonad. In preparation for fertilization, germ cells undergo gametogenesis, which includes meiosis, to reduce the number of chromosomes and cytodifferentiation to complete their maturation.
Figure 2.1.An embryo at the end of the third week, showing the position of PGCs in the wall of the yolk sac, close to the attachment of the future umbilical cord.
From this location, these cells migrate to the developing gonad.
Primordial Germ Cells and Teratomas
Teratomas are tumors of disputed origin that often contain a variety of tissues, such as bone, hair, muscle, gut epithelia, and others. It is thought that these tumors arise from pluripotent stem cells that can differentiate into any of the three germ layers or their derivatives. Some evidence suggests that PGCs that have strayed from their normal migratory paths could be responsible for some of these tumors (Fig. 2.2). Another source may be epiblast cells that give rise to all three germ layers during gastrulation (See Fig. 5.9).
Figure 2.2.Oropharnyngeal teratoma.
These tumors may arise from PGCs or from epiblast cels (see Chapter 5), both of which are pluripotent. Tissues within the tumors include derivatives of all three germ layers and may include gut, bone, skin, teeth, and so forth.
The Chromosome Theory of Inheritance
Traits of a new individual are determined by specific genes on chromosomes inherited from the father and the mother. Humans have approximately 23,000 genes on 46 chromosomes. Genes on the same chromosome tend to be inherited together and so are known as linked genes. In somatic cells, chromosomes appear as 23 homologous pairs to form the diploid number of 46. There are 22 pairs of matching chromosomes, the autosomes, and one pair of sex chromosomes. If the sex pair is XX, the individual is genetically female; if the pair is XY, the individual is genetically male. One chromosome of each pair is derived from the maternal gamete, the oocyte, and one from the paternal gamete, the sperm. Thus, each gamete contains a haploid number of 23 chromosomes, and the union of the gametes at fertilization restores the diploid number of 46.
Mitosis is the process whereby one cell divides, giving rise to two daughter cells that are genetically identical to the parent cell (Fig. 2.3). Each daughter cell receives the complete complement of 46 chromosomes. Before a cell enters mitosis, each chromosome replicates its deoxyribonucleic acid (DNA). During this replication phase, chromosomes are extremely long, they are spread diffusely through the nucleus, and they cannot be recognized with the light microscope. With the onset of mitosis, the chromosomes begin to coil, contract, and condense; these events mark the beginning of prophase. Each chromosome now consists of two parallel subunits, chromatids, that are joined at a narrow region common to both called the centromere. Throughout prophase, the chromosomes continue to condense, shorten, and thicken (Fig. 2.3A), but only at prometaphase do the chromatids become distinguishable (Fig. 2.3B). During metaphase, the chromosomes line up in the equatorial plane, and their doubled structure is clearly visible (Fig. 2.3C). Each is attached by microtubules extending from the centromere to the centriole, forming the mitotic spindle. Soon, the centromere of each chromosome divides, marking the beginning of anaphase, followed by migration of chromatids to opposite poles of the spindle. Finally, during telophase, chromosomes uncoil and lengthen, the nuclear envelope reforms, and the cytoplasm divides (Fig. 2.3D,E–F). Each daughter cell receives half of all doubled chromosome material and thus maintains the same number of chromosomes as the mother cell.
Figure 2.3.Various stages of mitosis.
In prophase, chromosomes are visible as slender threads. Doubled chromatids become clearly visible as individual units during metaphase. At no time during division do members of a chromosome pair unite. Blue, paternal chromosomes; red, maternal chromosomes.
Meiosis is the cell division that takes place in the germ cells to generate male and female gametes, sperm and egg cells, respectively. Meiosis requires two cell divisions, meiosis I and meiosis II, to reduce the number of chromosomes to the haploid number of 23 (Fig. 2.4). As in mitosis, male and female germ cells (spermatocytes and primary oocytes) at the beginning of meiosis I replicate their DNA so that each of the 46 chromosomes is duplicated into sister chromatids. In contrast to mitosis, however, homologous chromosomes then align themselves in pairs, a process called synapsis. The pairing is exact and point for point except for the XY combination. Homologous pairs then separate into two daughter cells, thereby reducing the chromosome number from diploid to haploid. Shortly thereafter, meiosis II separates sister chromatids. Each gamete then contains 23 chromosomes.
Figure 2.4.First and second meiotic divisions.
A. Homologous chromosomes approach each other. B. Homologous chromosomes pair, and each member of the pair consists of two chromatids. C. Intimately paired homologous chromosomes interchange chromatid fragments (crossover). Note the chiasma. D. Double-structured chromosomes pull apart. E. Anaphase of the first meiotic division. F, G. During the second meiotic division, the double-structured chromosomes split at the centromere. At completion of division, chromosomes in each of the four daughter cells are different from each other.
Crossovers, critical events in meiosis I, are the interchange of chromatid segments between paired homologous chromosomes (Fig. 2.4C). Segments of chromatids break and are exchanged as homologous chromosomes separate. As separation occurs, points of interchange are temporarily united and form an X-like structure, a chiasma (Fig. 2.4C). The approximately 30 to 40 crossovers (one or two per chromosome) with each meiotic I division are most frequent between genes that are far apart on a chromosome.
As a result of meiotic divisions:
- Genetic variability is enhanced through
- crossover, which redistributes genetic material
- random distribution of homologous chromosomes to the daughter cells
- Each germ cell contains a haploid number of chromosomes, so that at fertilization the diploid number of 46 is restored.
Also during meiosis, one primary oocyte gives rise to four daughter cells, each with 22 plus 1 X chromosomes (Fig. 2.5A). Only one of these develops into a mature gamete, however, the oocyte; the other three, the polar bodies, receive little cytoplasm and degenerate during subsequent development. Similarly, one primary spermatocyte gives rise to four daughter cells, two with 22 plus 1 X chromosomes and two with 22 plus 1 Y chromosomes (Fig. 2.5B). In contrast to oocyte formation, however, all four develop into mature gametes.
Figure 2.5.Events occurring during the first and second maturation divisions.
A. The primitive female germ cell (primary oocyte) produces only one mature gamete, the mature oocyte. B. The primitive male germ cell (primary spermatocyte) produces four spermatids, all of which develop into spermatozoa.