Research Questions

What can we learn about evolutionary adaptation to gravity by exploiting the weightlessness of spaceflight and the relative plasticity of early developing organisms?

The lower life forms, e.g., bacteria, protozoa, and invertebrates, are relatively independent of the force of gravity in their development, at least as determined by hypergravity studies using centrifuges. They are also relatively insensitive to radiation. The vertebrate embryo, on the other hand, is more sensitive to disturbing environmental parameters. Even very slight increases in gravity are known to affect vertebrate development. Satisfactorily experimental designs can now be implemented on board the Space Shuttle or the ISS to answer questions concerning the effect of microgravity on very early development of the more primitive vertebrates, the cold blood animals. In fact, the results of some of these experiments are reported in Chapter 5.

The warm blood animals, i.e., the birds and mammals, demand more time for developmental studies than the present Space Shuttle mission durations ranging from 11-14 days. The chicken egg takes 21 days to hatch, with a total of about 23 days after fertilization. Many rodents have about a 22-day gestation period while the more advanced mammals have month-long gestation periods. The minimum requirements for a rat development experiment are not even met by the 21-day flight of a Russian biosatellite. Some answers for vertebrate development questions can only be obtained by experiments on board the ISS.

Life cycle studies of lower forms, e.g., insects, can benefit from the shorter missions of the Space Shuttle. However, longer duration flights can afford exposure of many more generations to the space environment. Thus the prospects of adaptation and expression of mutations increase. The longer the mission, the more advanced the life forms that can experience a complete life cycle.

Even more interesting from the standpoint of gravity effects would be the use of the more gravity-sensitive, larger, and more advanced animals. A one-year long mission, for instance, would permit the successive development of as many as four generations of a rodent. The importance of the mechanics of post-gestation development, e.g., nursing, feeding, drinking, and maternal behavior, can be effectively studied under low-g conditions. If mating behavior can take place in a microgravity environment becomes also an important question in the frame of very long duration mission or space colonization.

The ISS provides ideal conditions with a long-term exposure to microgravity, associated with closely controlled systems of isolation and sensory deprivation with tight environmental tolerances (light, temperature, noise). Therefore, of primary interest are the studies on circadian rhythms, which are cycles of about a day, as for example the sleep and rest cycle. Most animals have some kind of biorhythms, and studies describing and attempting to explain them with diverse animal and plant species are relevant to the biomedical implications of human circadian rhythmicity, such as blood pressure cycles, drug susceptibility, sleep/wakefulness, and jet lag. Of more basic interest are those studies concerned with effectors, cues, and inherent oscillators operant in circadian control of physiological and behavioral function. Logical candidates for flight biorhythm studies are Drosophila, mice, and rats.

The effects of spaceflight on the neurons of the brain that constitute the internal clock can be studied by measuring Immediate Early Gene (IEG) activation in response to light/dark stimuli. IEGs, a newly discovered class of intracellular messengers, contain instructions for the production of proteins. These genes are unique in that they respond very early to stimuli. While there are many families of IEGs, the action of each family is evoked by different stimulation. Two families, known as c-fos and jun-B, are of interest because they are activated by neuronal activity, and, as such, serve as early markers of neuronal plasticity. By identifying the presence and production of IEGs in microgravity, scientists can determine where in the brain plasticity is occurring. In biorhythm studies, scientists can measure the levels of these early genes products, as well as the expression of IEGs in the brain structures involved in the regulation of the sleep-wake cycle (Fuller et al. 2003).

Ground

Figure 1-18. Division in amphibian (pleurodele newt) eggs, showing some abnormalities (larger sillons, odd number of cells) in the flight specimens by comparison to ground controls. Adapted from Gualandris-Parisot et al. (2002).

Flight

Figure 1-18. Division in amphibian (pleurodele newt) eggs, showing some abnormalities (larger sillons, odd number of cells) in the flight specimens by comparison to ground controls. Adapted from Gualandris-Parisot et al. (2002).

Consequently, developmental biology research in space is one of the most promising areas of investigation for both the ISS program and for biomedical concerns on Earth. In fact, there are presently a variety of exciting and innovative studies in the area of development. For example, space research has proven that rapidly developing and growing bodies are even more sensitive to the effects of weightlessness than are mature adults, thus providing more dramatic and rapidly established models of how gravity affects the formation and maintenance of bone, muscle, and cardiovascular function. We know that calcium crystals in the otoliths of the inner ear form differently in the weightless environment of space. New questions about the developmental programs that form this sensory system and others, and their connections to the brain can be investigated. So, it is of great importance to make use of the microgravity environment for studying the role of gravity-sensing mechanisms in the normal anatomical, physiological, and behavioral development.

Also of great interest is the influence of gravity during and after egg fertilization, and over the early course of embryonic development. Many of the mechanisms underlying early developmental processes are still unknown. The same holds true for influences exerted by environmental factors in critical stages of embryogenesis. For example, radical changes in the structure and connections of neurons occur during the development of the nervous system. From the tissue layers found in embryonic animals, cells increase in number and eventually differentiate and migrate to their appropriate function and position in the developing nervous system. In all, up to 75% of neurons are lost by the process of apoptosis, or programmed cell death, during development. Those that remain must form synapses with communicating neurons to serve their function in the adult nervous system. Because these processes are regulated by both chemical and mechanical factors, gravity may play a crucial role as a stimulus for proper development of the nervous system.

The notion that environmental input is essential during critical periods of development is not new. Young animals deprived of opportunities to see or walk during the first one to two weeks of life never see or learn to walk correctly, respectively. Thus experience can dictate development. By studying the development of mammals, it is possible to learn how genetic determination and experience interact to define the capabilities of the adult nervous system (Walton et al. 2003).

Certain well-known effects on amphibian eggs induced by changes in the gravitational vector make it important to also investigate whether early mammalian development processes are gravity-sensitive and thus may be disturbed in the 0-g environment. Of special interest is the possibility that gravitational forces might modify the morphogenetic pattern in its earliest and most fundamental manifestations, such as polarity and bilateral symmetry.

Manipulation of fertilized frog eggs, by which the heavy yolk is forced to maintain an upward instead of downward position, has been shown to initiate abnormal development (Figure 1-18). Also, exaggeration of the force of gravity by centrifugation has been shown to interfere with morphogenesis in amphibians when applied at a sensitive stage of the developmental process.

Thus, the space environment, and particularly microgravity, is a unique tool in the study of early developmental mechanisms (Table 1-05). Indeed, we do not know if normal embryonic development is possible in this condition. Is the spatial orientation of the plane of cleavage division affected by the line of reference provided by the gravitational vector? If the predominance of a given initial plane of cleavage is weakened by the absence of effective gravity, could this lead to an abnormal embryonic development?

Current

Amphibian early embryogenesis

Mammalian fertilization

Gravitosensing organs morphology and development

Future

Cell differentiation, cell/tissue competence

Gravitosensing organs/tissues:

Threshold of sensitivity

Developmental period of sensitivity

Information processing

Chemistry and physical properties

Evolution

Developmental timing

Organ development

Gametogenesis

Birth and mating in microgravity

Effect of gravity on life cycle

Maturation

Table 1-05. Current andfuture space research in Developmental Biology.

Table 1-05. Current andfuture space research in Developmental Biology.

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