The Questions of Developmental Biology

Neural regeneration
While the central nervous system is characterized by its ability to change and make new
connections, it has very little regenerative capacity. However, the peripheral nervous system,
especially the motor neurons, has significant regenerative powers, even in adult mammals.
The regeneration of motor neurons involves regrowing a severed axon, not replacing a missing or
diseased cell body. If the cell body of a motor neuron is destroyed, it cannot be replaced.
The myelin sheath that covers the axon is necessary for its regeneration. This sheath is made by
the Schwann cells, a type of glial cell in the peripheral nervous system (see Chapter 12). When an
axon is severed, the Schwann cells divide to form a pathway along which the axon can grow from
the proximal stump. This proliferation of the Schwann cells is critical for directing the
regenerating axon to the original Schwann cell basement membrane. If the regrowing axon can
find that basement membrane, it can be guided to its target and restore the original connection.
The regenerating neuron secretes mitogens that allow the Schwann cells to divide. Some of these
mitogens are specific to the developing or regenerating nervous system (Livesey et al. 1997).
The neurons of the central nervous system cannot regenerate their axons under normal
conditions. Thus, spinal cord injuries can cause permanent paralysis. As mentioned in Chapter 12,
one strategy to get around this block is to find ways of enlarging the population of neural stem
cells and to direct their development in ways that circumvent the lesions caused by disease or
trauma. The neural stem cells found in adult mammals may be very similar to embryonic neural
stem cells and can respond to the same growth factors (Johe et al. 1996; Johansson et al. 1999).
Another strategy for CNS neural regeneration is to create environments that encourage axonal
growth. Unlike the Schwann cell of the peripheral nervous system, the myelinating cell of the
central nervous system, the oligodendrocyte, produces substances that inhibit axon regeneration
(Schwab and Caroni 1988). Schwann cells transplanted from the peripheral nervous system into a
CNS lesion are able to encourage the growth of CNS axons to their targets (Keirstead et al. 1999;
Weidner et al. 1999).
Two substances that are inhibitory to neuron outgrowth have been isolated from
oligodendrocyte myelin. The first is myelin-associated glycoprotein; the second is Nogo-1
(Mukhopadyay et al. 1994; Chen et al. 2000; GrandPré et al 2000). Antibodies against Nogo-1
allow partial regeneration after spinal cord injury (Schnell and Schwab 1990).
Research into CNS axon regeneration may become one of the most important contributions of
developmental biology to medicine.
Aging: The Biology of Senescence
Entropy always wins. Each multicellular organism, using energy from the sun, is able to
develop and maintain its identity for only so long. Then deterioration prevails over synthesis, and
the organism ages. Aging can be defined as the time-related deterioration of the physiological
functions necessary for survival and fertility. The characteristics of aging as distinguished from
diseases of aging (such as cancer and heart disease) affect all the individuals of a species.
Many evolutionary biologists (Medawar 1952; Kirkwood 1977) would deny that aging is
part of the genetic repertoire of an animal. Rather, they would consider aging to be the default
state occurring after the animal has fulfilled the requirements of natural selection. After its
offspring are born and raised, the animal can die. Indeed, in many organisms, from moths to
salmon, this is exactly what happens. As soon as the eggs are fertilized and laid, the adults die.