Chapter 3: Figure and Ground
47 - Understanding Eggs (Part Two)
As formerly independent life forms, mitochondria have their own genes. And they inhabit the cell’s cytoplasm, which is to say they live outside of that cell’s nuclear DNA. Moreover, mitochondria are inherited largely from the mother. In a developing mouse embryo, for example, those inherited from the mother outnumber the father’s by a ratio of ten thousand to one. But as mitochondria are drawn into the earliest stages of an embryo’s development, something that affects it in major ways can happen.
Development begins with a process in which there is no actual growth. What happens instead is that the egg is repeatedly cleaved into a ball of increasingly smaller cells, each of which is complete and has its own copy of the nuclear DNA. These are the embryonic stem cells of recent debate.
As that process reaches its end, a dramatic new set of changes called gastrulation begins. In it, separate zones of cells form, which will with time become the different organs, and those zones begin to migrate to an early approximation of where they’ll be in the body. This extraordinary involution—in which various zones dive into the center, roll to the surface, or shear into layers—is akin to a ball turning itself inside out. “It is not birth, marriage, or death, but gastrulation,” says biologist Lewis Wolpert, “which is truly the most important time in your life.”
This is no less so because it’s then that a damaged mitochondrion—which can get shunted into specific cells during cleavage—may then become endemic to specific cell zones. Later, once those zones develop into organs, like the eyes and pancreas, their damaged mitochondria cause the disease called diabetes. Or so recent studies claim. In the past two decades, geneticists have suggested hundreds of links between mitochondrial mutations and specific human problems. Along with diabetes they include deafness, speech defects, shortness, mental retardation, and strokes. And in every case their origins stem from mitochondria, which, as noted, are separate from the embryo’s nuclear DNA.
But the egg cytoplasm has another, more significant influence on development. That influence is coded in patterns the mother lays down there, and to which the growing embryo conforms. Nuclear DNA is often described as a kind of blueprint, but that’s fundamentally misleading. As Wolpert puts it:
A descriptive program, like a blueprint or a plan, describes an object in some detail. A generative program describes how to make an object. For the same object the two programs are very different. Consider Origami, the Japanese art of paper folding. By folding a piece of paper in various directions it is quite easy to make a paper hat or a bird from a single sheet. To describe in any detail the final form of the paper, with the complex relationships between its parts, is really very difficult, and not of much help in explaining how to achieve that. Much more useful and easier to formulate are instructions on how to fold the paper. The reason for this is that simple instructions about folding have complex spatial consequences. In development, gene action similarly sets in motion a sequence of events that can bring about profound changes in the embryo. One can thus think of the genetic information in the fertilized egg as equivalent to the folding instruction in Origami—both contain a generative program for making a particular structure.
In lower life forms such as fruit flies, the embryo’s nuclear “generative program” expands out into the surrounding cytoplasm (whereas in mammals the nucleus and cytoplasm both cleave to form the start of an embryo). In either case, as an embryo accelerates through the wrenching transformations of cleavage and gastrulation, and begins the process of forming actual organs, it is also being shaped by structures found only in the cytoplasm of the egg.
For instance, all complex life forms have in common the tendency to take shape around an axis. Plants have tips and roots, animals have head (anterior) and tail (posterior) ends. The development of fruit flies—the workhorses, so to speak, of embryo research—illustrates a principle common to most developing animals. Maternal genes and proteins are transmitted to various regions of the cytoplasm by the mother fly. That happens as the egg is being formed. And these set a pattern of “positional information” that then triggers certain genes inside the expanding embryo.
As those genes are activated, a cascade effect takes place in the embryo. First, three broad domains form. Then—as the cascade continues and new genes are successively brought into play—smaller domains form within those three. Conceptually, these come to resemble a row of zebra-striped segments across the body’s axis. That axis is another characteristic set by genes and proteins in the cytoplasm. The axis appears to be oriented by a gradient there, the various shades of which determine what will become the anterior and posterior regions of the body. Among the proteins found in the anterior region of the cytoplasm is one called bicoid. In a study that sounds less like science than fiction, bicoid was injected into various locations of developing eggs. Wherever it came into contact with the embryonic fly’s developing body, that’s where the head grew.
The influence from mitochondria and the shaping of overall body plan are just two in a growing list of ways that factors outside an embryo’s nuclear DNA can affect its growth and form. Those factors also seem to pace the rhythm of each new pulse of cell divisions during cleavage and to guide the migration of cell zones in gastrulation. Biologist Mae-Wan Ho has called the development process “a true communication channel” between the environment and nuclear genes. Maternal and cytoplasmic effects, Ho adds, provide that link. The cytoplasm is both a “carrier of heredity,” quite apart from the nuclear genes of the developing embryo, and “the necessary interface between [those] nuclear genes and the environment, in the coordination of developmental and evolutionary processes.”
Until recently those were fighting words among specialists in these fields. They signaled a fundamental shift. Received wisdom since the 1930s had coalesced around the neo-Darwinist view, the dogma of unfettered nuclear DNA authority. But as one critic has pointed out, if development is nothing more than the outgrowth of nuclear DNA, “it would be the only example found in nature of a biological process devoid of feedback.”
Email this to a friend | 
Add to del.icio.us | 
Add to digg |
Linkology by Kate (all links are unofficial) | Rights Info
