The Questions of Developmental Biology

*The tradition of leaving one's books and classrooms and going directly to nature is very strong in developmental
biology. There is a sign at Woods Hole Marine Biological Laboratory, the scene of some of the most important
embryological research in America. The sign, attributed to Louis Agassiz, reads, "Study Nature, Not Books." It hangs
at the entrance to the library.
This thrombin-produced factor has not yet been isolated. But it is not the only difference between urodele and
mammalian limbs. Another difference is that salamanders retain Hox gene expression in their appendages even when
they are adults. It should be noted that, although most of the regeneration blastema comes from the dedifferentiation of
the tissue at the edge of the stump, another source of cells is also possible. While multinucleated skeletal muscle tissue
will dedifferentiate and supply uncommitted mononucleated cells to the blastema, the limb also contains muscle
satellite cells mononucleated cells committed to the muscle lineage that may be used during regeneration. Thus,
the regenerated limb's muscles may come from both the blastema and from these reserve cells.
The Hydra is another character from Greek mythology. Whenever one of this serpent's many heads was chopped off, it
regenerated two new ones. Hercules finally defeated the Hydra by cauterizing the stumps of its heads with fire.
Hercules had a longstanding interest in regeneration, for he was also the hero who finally freed the bound Prometheus,
thus stopping his daily hepatectomies.
Medical Advances in Regeneration
Humans do not regenerate their organs. Children can regenerate their fingertips, but even
this ability is lost in adults. The ability to regenerate damaged human organs would constitute a
medical revolution. Researchers are attempting to find ways of activating in the adult
developmental programs that were used during organogenesis. One avenue of this research
program is a search for stem cells that are still relatively undifferentiated, but which can form
particular cell types if given the appropriate environment (see Chapters 4 and 12). The second
avenue is a search for the environments that will allow such cells to initiate cell and organ
formation. We will look at two of these medical efforts.
Bone regeneration
While fractured bones can heal, bone
cells in adults usually do not regrow to bridge
wide gaps. The finding (Vortkamp et al. 1998)
that the same paracrine and endocrine factors
involved in endochondral ossification are also
involved in fracture repair raises the possibility
that new bone could grow if the proper paracrine
and extracellular environment were provided.
The problem is how to deliver these compounds
to a particular location over a long period of
time. One solution to the problem of delivery
was devised by Bonadio and his colleagues
(1999). They developed a collagen gel
containing plasmids carrying the human
parathyroid hormone gene. The plasmid-impregnated gel was placed
between the gaps of a broken dog tibia or femur. As cells migrated
into the collagen matrix, they incorporated the plasmid and made
parathyroid hormone. A dose-dependent increase in new bone
formation was seen in about a month (Figure 18.34). This type of
treatment has potential to help people with large bone fractures as
well as those with osteoporosis.